Method for drying a stent

ABSTRACT

Various embodiments of methods and devices for coating stents are described herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to methods and devices for coating stents.

2. Description of the State of the Art

This invention relates to radially expandable endoprostheses, that areadapted to be implanted in a bodily lumen. An “endoprosthesis”corresponds to an artificial device that is placed inside the body. A“lumen” refers to a cavity of a tubular organ such as a blood vessel. Astent is an example of such an endoprosthesis. Stents are generallycylindrically shaped devices, that function to hold open and sometimesexpand a segment of a blood vessel or other anatomical lumen such asurinary tracts and bile ducts. Stents are often used in the treatment ofatherosclerotic stenosis in blood vessels. “Stenosis” refers to anarrowing or constriction of a bodily passage or orifice. In suchtreatments, stents reinforce body vessels and prevent restenosisfollowing angioplasty in the vascular system. “Restenosis” refers to thereoccurrence of stenosis in a blood vessel or heart valve after it hasbeen treated (as by balloon angioplasty, stenting, or valvuloplasty)with apparent success.

Stents are typically composed of scaffolding that includes a pattern ornetwork of interconnecting structural elements or struts, formed fromwires, tubes, or sheets of material rolled into a cylindrical shape.This scaffolding gets its name because it physically holds open and, ifdesired, expands the wall of the passageway. Typically, stents arecapable of being compressed or crimped onto a catheter so that they canbe delivered to and deployed at a treatment site. Delivery includesinserting the stent through small lumens using a catheter andtransporting it to the treatment site. Deployment includes expanding thestent to a larger diameter once it is at the desired location.Mechanical intervention with stents has reduced the rate of restenosisas compared to balloon angioplasty. Yet, restenosis remains asignificant problem. When restenosis does occur in the stented segment,its treatment can be challenging, as clinical options are more limitedthan for those lesions that were treated solely with a balloon.

Stents are used not only for mechanical intervention but also asvehicles for providing biological therapy. Biological therapy usesmedicated stents to locally administer a therapeutic substance.Effective concentrations at the treated site require systemic drugadministration which often produces adverse or even toxic side effects.Local delivery is a preferred treatment method because it administerssmaller total medication levels than systemic methods, but concentratesthe drug at a specific site. Local delivery thus produces fewer sideeffects and achieves better results.

A medicated stent may be fabricated by coating the surface of a stentwith an active agent or an active agent and a polymeric carrier. Thoseof ordinary skill in the art fabricate coatings by applying a polymer,or a blend of polymers, to the stent using well-known techniques. Such acoating composition may include a polymer solution and an active agentdispersed in the solution. The composition may be applied to the stentby immersing the stent in the composition or by spraying the compositiononto the stent. The solvent then evaporates, leaving on the stentsurfaces a polymer coating impregnated with the drug or active agent.

Accurately loading drugs, minimizing coating defects, and coating withpure coating materials favor improved coating quality. In addition,adequate throughput of the overall manufacturing process is also ofconcern.

SUMMARY OF THE INVENTION

One aspect of the present invention is directed to embodiments of amethod of drying a stent that may include disposing a stent in achamber. The stent may have a coating material including a polymer and asolvent applied to a surface of the stent. The method may furtherinclude directing a fluid stream at the stent to remove at least aportion of the coating material, measuring a temperature of the fluid ata location adjacent to the stent, and controlling a temperature of thefluid stream based on the measured temperature so as to maintain adesired temperature adjacent to the stent.

A stent drying apparatus, which may include a chamber configured toreceive a stent having coating material including a polymer and asolvent, is also disclosed. The chamber may be adapted to receive afluid stream that contacts the coated stent. In some embodiments, thefluid stream removes at least a portion of the coating material. Atemperature sensor may be positioned adjacent to the stent for measuringthe temperature of the fluid stream-contacting the stent. The apparatusmay further include a controller connected to the sensor, wherein thecontroller adjusts a temperature of the fluid stream based on themeasured temperature so as to maintain a desired temperature of thefluid stream contacting the stent.

Other aspects of the present invention are directed to embodiments of afixture for supporting a stent during weighing that may include a panthat can support a stent greater than about 28 mm in length along thestent's entire length. Pan geometry may be optimized to minimize fixturemass.

A method of coating a stent comprising the step of modifying the flowrate of a coating material sprayed onto the stent while axially movingthe stent is also disclosed. In these or other embodiments, the stentrepeatedly passes from one end of the stent to another relative to amajor axis of the stent adjacent to a fixed or movable spray nozzle.Some of these methods further include adjusting the axial speed duringspraying of the stent based on the modified flow rate of the coatingmaterial to deposit a selected amount of coating material per pass.

Additional embodiments of invention coating methods include spraying acoating material from a nozzle onto a stent substantially concurrentlywith axially moving the stent. This axial movement causes the stent topass repeatedly from one end of the stent to another. The method mayfurther include controlling the rate of the movement to deposit aselected amount of coating material per pass.

In these or other embodiments, the method may include increasing theflow rate of material sprayed onto the stent as the stent is movedaxially. The method may further include adjusting the stent's speedbased on the increased flow rate to deposit a selected amount of coatingmaterial on the stent.

A method of coating a stent that includes increasing the flow rate ofmaterial sprayed onto a stent in which the stent is axially translatedrelative to the sprayed coating material during spraying of the stent.The motion causes the stent to pass repeatedly from one end of the stentto another. The method may further include adjusting the axialtranslation speed of the stent based on the increased flow rate of thecoating material to deposit a selected amount of material per pass.

A stent coating device that includes a first support element forrotating a first end of a stent and a second support element forrotating a second end of the stent, wherein the first and second ratesof rotation are the same as or different from each other is disclosed.

A device for coating a stent that includes a support element forrotating a stent, wherein the support element is capable of providing atleast one pulse in a rotation rate of the support element during stentcoating is also disclosed.

Other device embodiments are disclosed. For instance, a device that mayinclude a stent support element is disclosed. The element may be capableof providing at least one pulse in the rate of axial motion of the stentduring coating of the stent, wherein the pulse allows the supportelement to move axially relative to the stent.

Additional devices for coating stents may include a support element forrotating the stent. In these or other embodiments, the element includesat least three elongate arms converging inwardly from a proximal end toa distal end to form a conical or frusto-conical shape. The supportelement may be capable of being positioned within an end of a stentduring coating.

Further aspects of the present invention are directed to embodiments ofa method of coating a stent that may include rotating a stent with afirst rotatable element supporting a proximal end of the stent and asecond rotatable element supporting a second end of the stent. The firstrotatable element may rotate at a different rate than the secondrotatable element at least a portion of a time during coating of thestent.

Another aspect of the present invention is directed to embodiments of amethod of coating a stent that may include rotating a stent with arotatable element supporting at least a portion of a stent. The methodmay further include providing at least one pulse in a rotation rate ofthe rotatable element during coating of the stent.

Other aspects of the present invention are directed to embodiments of amethod of coating a stent that may include rotating a stent with a firstrotatable element supporting a proximal end of the stent and rotatingthe stent with a second rotatable element supporting a distal end of thestent, the first rotatable element having the same rotation rate as thesecond rotatable element. The method may further include providing atleast one pulse in a rotation rate of the first rotatable element duringcoating of the stent, the first rotatable element having a rotation ratedifferent from the second rotatable element during the pulse, the pulsecausing the first rotatable element to rotate relative to the stent.

Some aspects of the present invention are directed to embodiments of amethod of coating a stent that may include positioning a support elementwithin an end of a stent to support the stent. The method may furtherinclude providing at least one translational pulse to the supportelement along an axis of the stent during coating of the stent, wherebythe translational pulse causes the support element to move axiallyrelative to the stent.

Other aspects of the present invention are directed to embodiments of amethod of coating a stent that may include rotating a stent with asupport element having at least three elongate arms converging inwardlyfrom a proximal end to a distal end of each arm to form a conical orfrusto-conical shape, the support element positioned so that theelongate arms converge inwardly within an end of the stent to supportthe stent.

Certain aspects of the present invention are directed to embodiments ofa method of coating a stent that may include contacting a first axialportion of a stent with a support element such that a second axialportion does not contact the support element or any other supportelement. The method may further include applying a coating material tothe second axial portion and inhibiting or preventing application of thecoating material on the first axial portion.

Certain aspects of the present invention are directed to embodiments ofan apparatus for supporting a stent that may include a first support rodfor supporting a proximal end of a stent, the first support rod coupledto a first collet opposite the proximal end of the stent. The apparatusmay further include a second support rod for supporting a distal end ofthe stent, the second support rod coupled to a second collet oppositethe distal end of the stent. The apparatus may also include a thirdsupport rod for supporting the first collet and the second collet, thefirst collet being coupled to a proximal end of the third support rod,the second collet being coupled to a distal end of the third supportrod, wherein the third support rod extends between the first collet andthe second collet outside of and free of any contact with the stent.

Certain aspects of the present invention are directed to embodiments ofa device for supporting a stent that may include a filament having aspiral coiled portion, the coiled portion designed to support the stentat a plurality of contact points between the stent and the spiral coiledportion along a least a portion of an axis of the stent.

Certain aspects of the present invention are directed to embodiments ofa collet for supporting a stent during coating that may include agenerally tubular member having an end surface for contacting an end ofa stent. The end surface may include a projecting portion and a flat orrelatively flat portion. The projecting portion may include at leastthree segments radiating from a center of the end surface to an edge ofthe end surface, a thickness of the segments in a plane of the surfacedecreasing from the center to the edge of the end surface, and a heightof the projecting portion perpendicular to the plane of the surfacedecreasing from the center of the end surface to the edge.

Certain aspects of the present invention are directed to embodiments ofa stent support for supporting a stent during coating that may include agenerally tubular support member supporting a stent, the support elementhaving at least one magnetic element. The stent support may furtherinclude an electromagnetic device positioned adjacent to the mandrel forgenerating an electrical field that allows the magnetic element tosupport, rotate, and/or translate the mandrel.

Some aspects of the present invention are directed to embodiments of amethod of manufacturing an implantable medical device that includespurifying a polymer by: contacting the polymer with a fluid capable ofswelling the polymer and removing all or substantially all of the fluidfrom the polymer such that an impurity from the polymer is completely orat least partially removed by the fluid. The fluid may be selected fromthe group consisting of isopropyl acetate and propyl acetate. The methodmay further include coating an implantable medical device with thepurified polymer, or fabricating the implantable medical device frompurified polymer.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 depicts a three-dimensional view of a cylindrically-shaped stent.

FIG. 2A depicts a schematic embodiment of a drying apparatus.

FIG. 2B depicts a three-dimensional view of an embodiment of a chamberof the apparatus of FIG. 2A.

FIG. 2C depicts a radial cross-section of the chamber of FIG. 2B.

FIGS. 3A-C depict a weighing pan that can accommodate stents under 28 mmin length.

FIG. 4A depicts an embodiment of a weighing pan for a stent.

FIG. 4B depicts an overhead view of the pan of FIG. 4A.

FIG. 4C depicts an embodiment of a weighing pan for a stent.

FIGS. 5A-C depict embodiments of weighing pans with asymmetric shapesfor stents.

FIG. 6A depicts an embodiment of a cross-shaped weighing pan for astent.

FIG. 6B depicts an overhead view of the pan of FIG. 6A.

FIG. 6C depicts an embodiment of a cross-shaped weighing pan for astent.

FIG. 7 depicts an embodiment of a weighing pan with a ridge around itsedge.

FIG. 8 depicts an exemplary schematic embodiment of a spray coatingapparatus for coating a stent.

FIG. 9 depicts a mounting assembly for supporting a stent.

FIGS. 10A-D depict the rotation rate as a function of time forrepresentative pulses in rotation rate.

FIGS. 11A-B depict mounting assemblies for supporting a stent.

FIG. 12 depicts a representative linear pulse showing linear translationrate versus time.

FIGS. 13A-H depict the axial position of a support element as a functionof time.

FIG. 14A depicts an embodiment of a stent support system.

FIG. 14B depicts a close-up view of one side of the stent support systemof FIG. 14A.

FIG. 15A depicts a side view of an embodiment of a stent support systemfor coating a portion of a stent that has no contact points.

FIG. 15B depicts an axial cross-section of the stent support system ofFIG. 15A.

FIG. 16A depicts an alternative view of the stent support system of FIG.15A.

FIG. 16B depicts an axial cross-section of one side of the stent supportsystem of FIG. 16A.

FIG. 17A depicts an alternative view of the stent support system of FIG.15A.

FIG. 17B depicts an axial cross-section of one side of the stent supportsystem of FIG. 17A.

FIG. 18 depicts an embodiment for coating a central portion of a stentthat has no contact points.

FIG. 19A depicts an exemplary embodiment of a stent support system.

FIG. 19B depicts a close-up view of one side of the stent support systemof FIG. 19A.

FIG. 20 depicts a side view of an exemplary embodiment of a stentsupport system.

FIG. 21 depicts the stent support system of FIG. 19A coupled to arotatable spindle.

FIG. 22A depicts a two-dimensional view of a spiral coil support.

FIG. 22B depicts an illustration of a prototype of a spiral coilsupport.

FIG. 23A depicts a holder for manipulating and positioning a spiral coilsupport.

FIG. 23B depicts a radial cross-section of the front of the holder ofFIG. 23A.

FIG. 24A depicts a picture of a spiral coil support supported by aholder.

FIG. 24B depicts a picture illustrating a close-up view of a spiral coilsupport positioned within a stent.

FIG. 25 depicts an axial view of a system for coating a stent supportedby a spiral coil support.

FIGS. 26A-D depict scanning electron micrograph (SEM) images of 28 mmstents coated using a spiral coil support to support the stent duringcoating.

FIG. 27 depicts a stent mounted on a stent support system.

FIGS. 28A-D depict an exemplary embodiment of a collet.

FIGS. 29A-B depict photographs with side views of an embodiment of acollet according to the present invention.

FIGS. 29C-D depict photographs with overhead views of an embodiment of acollet according to the present invention.

FIG. 29E depicts a photograph with a view of an embodiment of a colletaccording to the present invention with a stent mounted on the collet.

FIG. 30 is an exemplary embodiment of a stent support system with amandrel capable of magnetic levitation.

FIG. 31 depicts an overhead view of a coating system illustratingstations corresponding to various processing steps.

FIG. 32 shows the swell percentage of a polymer sample in varioussolvents obtained by measuring the size of the sample at selected times.

FIG. 33 shows the swell percentage of a polymer sample in varioussolvents obtained by measuring the weight of the sample at selectedtimes.

DETAILED DESCRIPTION OF THE INVENTION

Embodiments of the present invention relate to coating implantablemedical devices such as stents. More generally, embodiments of thepresent invention may also be used in coating devices including, but notlimited to, self-expandable stents, balloon-expandable stents,stent-grafts, vascular grafts, cerebrospinal fluid shunts, pacemakerleads, closure devices for patent foramen ovale, and synthetic heartvalves.

In particular, a stent can have virtually any structural pattern that iscompatible with a bodily lumen in which it is implanted. Typically, astent is composed of a pattern or network of circumferential andlongitudinally extending interconnecting structural elements or struts.In general, the struts are arranged in patterns, which are designed tocontact the lumen walls of a vessel and to maintain vascular patency. Amyriad of strut patterns are known in the art for achieving particulardesign goals. A few of the more important design characteristics ofstents are radial or hoop strength, expansion ratio or coverage area,and longitudinal flexibility. Embodiments of the present invention areapplicable to virtually any stent design and are, therefore, not limitedto any particular stent design or pattern. One embodiment of a stentpattern may include cylindrical rings composed of struts. Thecylindrical rings may be connected by connecting struts.

In some embodiments, a stent may be formed from a tube by laser cuttingthe pattern of struts in the tube. The stent may, also be formed bylaser cutting a metallic or polymeric sheet, rolling the pattern intothe shape of the cylindrical stent, and providing a longitudinal weld toform the stent. Other methods of forming stents are well known andinclude chemically etching a metallic or polymeric sheet and rolling andthen welding it to form the stent.

In other embodiments, a metallic or polymeric filament or wire may alsobe coiled to form the stent. Filaments of polymer may be extruded ormelt spun. These filaments can then be cut, formed into ring elements,welded closed, corrugated to form crowns, and then the crowns weldedtogether by heat or solvent to form the stent.

FIG. 1 illustrates a conventional stent 10 formed from a plurality ofstruts 12. The plurality of struts 12 are radially expandable andinterconnected by connecting elements 14 that are disposed betweenadjacent struts 12, leaving lateral openings or gaps 16 between adjacentstruts 12. Struts 12 and connecting elements 14 define a tubular stentbody having an outer, tissue-contacting surface and an inner surface.

The cross-section of the struts in stent 10 may be rectangular- orcircular-shaped. The cross-section of struts is not limited to these,and therefore, other cross-sectional shapes are applicable withembodiments of the present invention. Furthermore, the pattern shouldnot be limited to what has been illustrated as other stent patterns areeasily applicable with embodiments of the present invention.

Coating a Stent

As indicated above, a medicated coating on a stent may be fabricated byspraying a coating composition including polymer and drug on the stent.Spray coating a stent typically involves mounting or disposing a stenton a support, followed by spraying a coating material from a nozzle ontothe mounted stent.

A spray apparatus, such as EFD 780S spray device with VALVEMATE 7040control system (manufactured by EFD Inc., East Providence, R.I., can beused to apply a composition to a stent. A EFD 780S spray device is anair-assisted external mixing atomizer. The composition is atomized intosmall droplets by air and uniformly applied to the stent surfaces. Othertypes of spray applicators, including air-assisted internal mixingatomizers and ultrasonic applicators, can also be used for theapplication of the composition.

To facilitate uniform and complete coverage of the stent during theapplication of the composition, the stent can be rotated about thestent's central longitudinal axis. Rotation of the stent can be fromabout 0.1 rpm to about 300 rpm, more narrowly from about 30 rpm to about200 rpm. By way of example, the stent can rotate at about 150 rpm. Thestent can also be moved in a linear direction along the same axis. Thestent can be moved at about 1 mm/second to about 12 mm/second, forexample about 6 mm/second, or for a minimum of at least two passes(i.e., back and forth past the spray nozzle).

A nozzle can deposit coating material onto a stent in the form of finedroplets. An atomization pressure of a sprayer can be maintained at arange of about 5 psi to about 30 psi. The droplet size depends onfactors such as viscosity of the solution, surface tension of thesolvent, and atomization pressure. The flow rate of the composition fromthe spray nozzle can be from about 0.01 mg/second to about 1.0mg/second, for example about 0.1 mg/second. Only a small percentage ofthe composition that is delivered from the spray nozzle is ultimatelydeposited on the stent. By way of example, when a composition is sprayedto deliver about 1 mg of solids, only about 100 micrograms or about 10%of the solids sprayed will likely be deposited on the stent.

Depositing a coating of a desired thickness in a single coating stagecan result in an undesirably nonuniform surface structure and/or coatingdefects. Therefore, the coating process can involve multiple repetitionsof spraying forming a plurality of layers. Each repetition can be, forexample, about 0.5 second to about 20 seconds, for example about 10seconds in duration. The amount of coating applied by each repetitioncan be about 1 microgram/cm² (of stent surface) to about 50micrograms/cm², for example less than about 20 micrograms/cm² per1-second spray.

As indicated above, the coating composition can include a polymerdissolved in a solvent. Each repetition can be followed by removal of asignificant amount of the solvent(s). In an embodiment, there may beless than 5%, 3%, or more narrowly, less than 1% of solvent remaining inthe coating after drying between repetitions. When the coating processis completed, all or substantially all of the solvent may be removedfrom the coating material on the stent. Any suitable number ofrepetitions of applying the composition followed by removing thesolvent(s) can be performed to form a coating of a desired thickness orweight. Excessive application of the polymer can, however, cause coatingdefects.

A stent coated with coating material can be dried by allowing thesolvent to evaporate at room or ambient temperature. Depending on thevolatility of the particular solvent employed, the solvent can evaporateessentially upon contact with the stent. Alternatively, the solvent canbe removed by subjecting the coated stent to various drying processes.Drying time can be decreased to increase manufacturing throughput byheating the coated stent. For example, removal of the solvent can beinduced by baking the stent in an oven at a mild temperature (e.g., 60°C.) for a suitable duration of time (e.g., 2-4 hours) or by theapplication of warm air. A stent is typically dried in an oven as thefinal drying step when the deposition stages are completed.

Evaporation of the solvent(s) can be induced by application of a warmgas between each repetition which can prevent coating defects andminimize interaction between the active agent and the solvent. The stentmay be positioned below a nozzle blowing the warm gas. A warm gas may beparticularly suitable for embodiments in which the solvent employed inthe coating composition is a non-volatile solvent (e.g.,dimethylsulfoxide (DMSO), dimethylformamide (DMF), and dimethylacetamide(DMAC)). The temperature of the warm gas can be from about 25° C. toabout 200° C., more narrowly from about 40° C. to about 90° C. By way ofexample, warm gas applications can be performed at a temperature ofabout 60° C., at a flow speed of about 5,000 feet/minute, and for about10 seconds.

The gas can be directed onto the stent following a waiting period ofabout 0.1 second to about 5 seconds after the application of the coatingcomposition so as to allow the liquid sufficient time to flow and spreadover the stent surface before the solvent(s) is removed to form acoating. The waiting period is particularly suitable if the coatingcomposition contains a volatile solvent since such solvents aretypically removed quickly. As used herein “volatile solvent” means asolvent that has a vapor pressure greater than 17.54 Torr at ambienttemperature, and “non-volatile solvent” means a solvent that has a vaporpressure less than or equal to 17.54 Torr at ambient temperature.

Any suitable gas can be employed, examples of which include air, argon,or nitrogen. The flow rate of the warm gas can be from about 20 cubicfeet/minute (CFM) (0.57 cubic meters/minute (CMM)) to about 80 CFM (2.27CMM), more narrowly about 30 CFM (0.85 CMM) to about 40 CFM (1.13 CMM).The warm gas can be applied for about 3 seconds to about 60 seconds,more narrowly for about 10 seconds to about 20 seconds. By way ofexample, warm air applications can be performed at a temperature ofabout 50° C., at a flow rate of about 40 CFM, and for about 10 seconds.

Drying

Regardless of the method used for drying a stent, it is important forthe drying process to be performed in a consistent manner for each layerand each stent. The same or similar processing conditions or parametersshould exist for each layer of coating material applied for each stent.The reason for this is that drying process parameters can influence themolecular structure and morphology of a dried polymer and drug coating.Drug release parameters depend upon on molecular structure andmorphology of a coating. Therefore, drug release parameters depend uponparameters of the drying process. For example, generally, the rate of adrying process is directly proportional to the resultant drug releaserate of a resultant coating.

Since the temperature of a drying process is directly related to therate of drying, it is important to control the drying temperature toobtain coating consistency. In general, the more consistent thetemperature during the drying process from layer to layer and stent tostent, the more consistent the resultant coating in a given stent andfrom stent to stent.

Various embodiments of a method and device for drying a stent in aconsistent manner are described herein. FIG. 2A depicts a schematicembodiment of an apparatus 100 for drying a coating material applied toan implantable medical device, such as a stent. Apparatus 100 includes achamber 102 configured to receive a stent having a coating materialapplied by a coating apparatus. FIG. 2B depicts a three-dimensional viewof an embodiment of chamber 102. As shown, chamber 102 iscylindrically-shaped. However, chamber 102 is not limited to the shapedepicted. In other embodiments, chamber 102 may be a conduit with across-section including, but not limited to, square, rectangular, ovaletc. A coated stent for drying can be inserted into a side opening 104in chamber 102. Side opening 104 can be positioned, for example, at anylocation on the surface of chamber 102 adjacent to a desired dryingposition within chamber 102.

Additionally, chamber 102 has a proximal opening 106 for receiving astream of heated fluid or gas, as shown by an arrow 110, and a distalopening 108 through which the fluid exits, as shown by an arrow 112. Thefluid may be an inert gas such as air, nitrogen, oxygen, argon, etc.

As shown in FIG. 2A, apparatus 100 further includes a heated fluidsource 114 that can include a heating element 116 for heating the fluidused for drying a coated stent. For example, fluid source 116 can be ablower with a heating coil. The temperature of the heated fluid may beadjusted by controlling the heat supplied by heating element 116.

FIG. 2C depicts a radial cross-section of chamber 104 along a line A-Ain FIG. 2A. A coated stent 118 is shown disposed over a support 120within chamber 102. Support 120 with stent 118 is disposed throughopening 104 and is positioned so that the heated fluid contacts stent118 to dry the coating. Stent 118 is secured by collets 122 on support120. Temperature sensors 124 and 126 are positioned adjacent to stent118 to measure the drying temperature of the applied coating.Temperature sensors 124 and 126 are positioned as close as possible tostent 118 without significantly disrupting the flow of heated fluid paststent 118. In one embodiment, there is no or substantially no offset ordifference in temperature between the drying temperature of the coatingon the stent and the temperature measured by sensors 124 and 126. Inother embodiments, sensors 124 and 126 are positioned far enough away sothat there is an offset in the measured temperature and the dryingtemperature. Such an offset can be taken into account in the controlsystem described below. Temperature sensors 124 and 126 can bethermistors, thermocouples, or any other temperature measuring devices.

Temperature sensor 124 measures the drying temperature to gatherfeedback (T_(F)) for controlling the drying temperature of stent 118.Sensor 124 is coupled to a control system 132 by a sensor wire 128. Anysuitable control system, such as a closed loop system, can be used formaintaining the drying temperature of the coating at a desiredtemperature (T_(D)). A temperature, T_(F), measured by sensor 124 istransmitted via wire 128 to control system 132. Control system 132compares T_(F) to T_(D) and then transmits a signal 134 to fluid source114. Signal 134 carries instructions to fluid source 114 to adjust thetemperature of the fluid stream supplied to chamber 102 if thedifference in temperature is larger than a selected tolerance. In someembodiments, the desired temperature T_(D) can be a function of time orthickness.

Temperature sensor 126 monitors a drying temperature of the stent thatis independent of a control system. A monitored temperature, T_(M), canbe transmitted by a temperature sensor wire 130 to a display or anautomated system (not shown). The control system, in some instances, maybe unable to maintain a desired drying temperature. For example, thedrying temperature may deviate substantially from a desired temperature.A user can be alerted to the deviation by a displayed T_(M) and takeappropriate action, such as shutting down the drying process anddiscarding the coated stent. Alternatively, an automated system can beconfigured to take appropriate action such as shutting down the dryingprocess.

Table 1 presents data for stents dried at two different temperaturesusing an embodiment of the drying apparatus discussed herein. Tendifferent sample runs were performed at each temperature. The stentswere Xience-V stents obtained from Guidant Corporation, Santa Clara,Calif. The coating runs included application of a primer layer and adrug-matrix or reservoir layer over the primer layer. The coatingmaterial for the primer layer was poly(n-butyl methacrylate) (PBMA) inan acetone/cyclohexanone solvent. The coating material for the reservoirlayer was poly(vinylidene fluoride-co-hexafluoropropene) copolymer(PVDF-HFP) (e.g., SOLEF 21508, available from Solvay Solexis PVDF,Thorofare, N.J.) in an acetone/cyclohexanone solvent.

Ten samples were dried at each temperature. Each sample was dried over a24 hour period. Table 1 provides the percentage of solvent releasedduring the drying period for each sample at each temperature.

As expected, a larger percentage of solvent was released at the highertemperature. At 35° C., approximately 72% to 77% of the solvent wasreleased from the stent samples and at 65° C. all or substantially allof the solvent was released. At 65° C., for samples 1, 4, 5, 7, and 9,the measured percentage released was greater than 100%. This is likelydue to errors in weighing the stent samples before and after drying. At35° C., the standard deviation was less than 4° C. and the percentcoefficient of variation (% CV) was less than 5° C. At 65° C., thestandard deviation and % CV were both less than 2° C. The relatively lowvalues of standard deviation and % CV suggest that the drying methodtends to dry stents relatively consistently.

TABLE 1 Percentage of solvent released from coated stent dried at twotemperatures over a 24 hour period. Stents Dried Stents Dried Sample at35° C. at 65° C. 1 72.23 101.66 2 74.56 97.76 3 74.31 97.52 4 72.54101.40 5 72.29 102.40 6 73.57 98.38 7 76.60 101.44 8 63.85 97.28 9 75.59100.53 10 74.02 98.47 Average 73.46 99.68 Standard Deviation 3.62 1.98 %CV 4.93 1.99

Weighing of Stents

The amount of coating material applied to a stent is typicallydetermined by comparing the weight of an uncoated and coated stent. Theweight of a coated stent can be taken to be the dry coating weight.Stents are typically weighed using a microbalance, for example, the UMX5Microbalance from Mettler-Toledo, Inc. of Columbus, Ohio. A sample to beweighed, such as a stent, is disposed on a weighing pan of coupled to abalance for weighing. The maximum capacity of the UMX5 Microbalanceincluding a weighing pan (including its support) is 2.1 g. The weight ofa coated stent is approximately 0.4 g. Therefore, the maximum weight ofa weighing pan and its support is about 1.7 g for the above-mentionedbalance.

Weighing pans that are currently available for microbalances have amaximum surface diameter of under about 28 mm. Therefore, such panscannot accommodate stents longer than about 28 mm without portions ofthe stent hanging over an edge of the pan. Hanging portions duringweighing are undesirable due to the risk of the stent rolling off thepan. Such pans also have a flat surface with no raised features thatfacilitate loading of the stent or reduce or prevent rolling off of thestent from the pan.

FIGS. 3A-C depict a prior art weighing pan 160 that can accommodatestents under 28 mm in length. Weighing pan 160 is circular with adiameter, D_(p), of 27.57 mm and has a top surface 162 for supporting astent. Weighing pan 160 is coupled to a support rod 164 on a bottomsurface (not shown). Support rod 164 is configured to be coupled with abalance. Surface 162 of weighing pan 160 is substantially flat and hasno features such as indentations or ridges. The weight of weighing pan160, Mettler Toledo, part number ME-211185, and support rod 164 isapproximately 1.2 g.

Stents over 28 mm in length are not accommodated by current weighingpans. However, increasing the diameter of the current weighing pans toaccommodate such stents may result in a weighing pan that exceeds theweighing capacity of a typical microbalance. What is needed is aweighing pan that can accommodate stents over 28 mm in length withoutexceeding the capacity of a typical microbalance.

Embodiments of the present invention relate to a fixture that includes aweighing pan for weighing stents that are greater than about 28 mm inlength. In one embodiment, a fixture for supporting a stent duringweighing may include a plate or pan. At least a portion of an area of asurface of the pan can support a stent greater than about 28 mm inlength along an entire length of the stent without end portions of thestent hanging over an edge of the pan. For example, a portion of an areaof the surface can support a 28 mm, 33 mm, or 38 mm stent along itsentire length. In certain embodiments, a geometry of the pan isoptimized to minimize a mass of the pan, and thus the fixture. Inparticular, the mass of the fixture may be optimized so that the weightof the fixture and a stent does not exceed the capacity of a selectedmicrobalance.

In one embodiment, the fixture may include a pan having a plurality ofholes in a surface of the pan to reduce the mass of the fixture. The panmay have a shape that includes, but is not limited to, circular, oval,rectangular, etc. The holes tend to reduce the mass of the pan whilestill allowing the surface of the pan to support a stent along itsentire length.

FIGS. 4A-C depict exemplary embodiments of a fixture for supporting astent. In FIGS. 4A-B, a fixture 170 has a circular pan 172 and a supportrod 174. FIG. 4A depicts a three-dimensional view and FIG. 4B depicts anoverhead view of pan 172. Pan 172 includes a plurality of holes 176which reduce the mass of pan 172 so that the mass of fixture 174 doesnot exceed the maximum capacity of a microbalance. Pan 172 has adiameter D_(p) that is large enough to support a stent over 28 mm inlength along its entire length. It is desirable for the holes in a panto be relatively evenly distributed to enhance the stability of thefixture.

The mass of a pan may be optimized to a desired mass by varying the sizeand number of holes. As the size of the holes decreases, the number ofholes required to reduce the mass of the pan a selected amountincreases. This is illustrated in FIG. 4C by an exemplary pan 178 withholes 180 which are smaller than holes 176 in pan 172. Pan 178 has alarger number of holes 180 than pan 172 has of holes 176.

In some embodiments, the pan of a fixture may have an asymmetric shapethat is longer along one axis, for example, an oval, rectangular, ordumbbell shape. The surface along the longer axis may be configured toaccommodate a stent greater than 28 mm in length along its entirelength. FIGS. 5A-C depict exemplary pans with asymmetric shapes whichinclude an oval pan 184, a rectangular pan 186, and a dumbbell-shapedpan 188. An axis A-A corresponds to a longer axis of the shapes in FIGS.5A-C. A length LA corresponds to the length along axis A-A. LA is longenough to support a stent greater than 28 mm. A length along a shorteraxis need not be long enough to support the stent. Pans 184, 186, and188 can include holes 185, 187, and 189, respectively, to furtheroptimize the mass of the pan.

As the asymmetry of a pan increases, a fixture may tend to become lessstable. Additionally, a stent has an increased risk of rolling off a panthat is highly asymmetric. A more stable geometry of the pan may includeat least two intersecting elongated portions. At least one of theintersecting portions may be adapted to support a stent greater 28 mm inlength along its entire length. FIGS. 6A-B depict a fixture 190 with across-shaped pan 194 supported by a support rod 192. Cross-shaped pan194 includes intersecting rectangular portions 196 and 198. A lengthL_(C) of rectangular portion 196 is long enough to support a stentlonger than about 28 mm along its entire length. The mass of thecross-shaped pan can further be optimized with holes. FIG. 6C depicts afixture 200 with a cross-shaped pan 202 with holes 204.

In some embodiments, a weighing pan may include surface features at oradjacent to at least a portion of an edge of the pan to facilitateplacement or removal of a stent on the pan. The features may alsoinhibit a stent from falling or rolling off the pan. For example, thefeatures may include, but are not limited to, ridges, bumps, orprotrusions along at least a portion of the pan. FIG. 7 depicts afixture 210 including a pan 212 with holes 220 supported by a supportmember 214. Pan 212 includes a ridge 216 extending all the way aroundthe edge of pan 212. Ridge 216 can also be discontinuous, i.e., ridge212 can include a series of discrete portions separated by gaps.

Improving Throughput of Coating Process

A further aspect of the present invention relates to manipulation ofspray coating parameters to obtain desired processing goals and coatingcharacteristics. Spray coating parameters that may be manipulated caninclude, but are not limited to, flow rate of coating material, axialtranslation speed of stent, rotation speed, nozzle height, andatomization pressure.

FIG. 8 depicts an exemplary schematic embodiment of a spray coatingapparatus 250 for coating a stent 252. A syringe pump 256 pumps coatingmaterial from a reservoir 254 that is in fluid communication with aspray nozzle 258. Nozzle 258 can be in fluid communication with pump 256through a hose 260. Nozzle 258 provides a plume 260 of coating materialfor depositing on stent 252. A flow rate of coating material provided bynozzle 258 can be varied by changing the pump rate of pump 256.

Stent 252 is supported by a stent support 262, such as a mandrel, othersupport devices known in the art, or support devices as describedherein. Support 262 is configured to rotate stent 252 about itscylindrical axis, as shown by an arrow 264. Support 262 is alsoconfigured to axially or linearly translate stent 252 with respect toplume 260, as shown by an arrow 266. In other embodiments, nozzle 258can be translated along the cylindrical axis of stent 252 rather than orin addition to axially translating stent 252.

Coating material is deposited on stent 252 as it is translated throughplume 260 from a proximal end 268 to a distal end 270 of stent 252.After a selected number of passes through plume 260, the depositedcoating material is allowed to dry or subjected to a drying processknown in the art or described herein prior to further deposition ofcoating material. The deposition and drying steps are repeated until adesired amount of coating material is deposited on stent 252.

One aspect of the present invention relates to increasing the rate ofthe coating process or increasing throughput of the coated stents whilemaintaining coating quality. In one embodiment, the rate of the coatingprocess can be increased by increasing the flow rate of coating materialthrough nozzle. This can be accomplished by increasing the pump rate ofcoating material, as described above. An increased flow rate of coatingmaterial increases the amount or mass of coating material deposited perunit time on the stent or per pass of the nozzle over the stent.

However, increasing the flow rate, and mass per pass, can havedeleterious effects on coating quality. First, an increased mass perpass can lead to defects in the coating, as well as inconsistencies inthe coating from layer to layer and stent to stent. Second, increasingthe mass per mass increases the drying time of the deposited coatingmaterial. Due to the increased drying time, there is an increasedlikelihood of the nozzle clogging between passes. Residual coatingmaterial in the nozzle can dry and reduce or prevent flow of coatingmaterial through the nozzle. Embodiments of the method described hereinallow an increase in throughput and flow rate of coating material whilemaintaining coating consistency resulting in an acceptable level ofdefects. In addition, the increased flow rate does not lead to anincrease in nozzle clogging.

Certain embodiments of a method of coating a stent may include modifyinga flow rate of coating material sprayed onto a stent by a coatingapparatus. The method may further include adjusting an axial translationspeed of the stent based on the modified flow rate during spraying ofthe coating material to obtain a selected amount of deposition ofcoating material per pass of the stent relative to the nozzle. In oneembodiment, an axial translation speed of the stent may be controlled toobtain a selected amount of deposition or mass per pass of coatingmaterial.

In an embodiment, the flow rate of the coating material directed at thestent from a nozzle of the coating apparatus may be increased. The axialtranslation speed may then be increased to compensate for the increasedflow rate. The increased axial translation speed tends to decrease themass per pass at the increased flow rate. The axial translation speedmay be increased so that the mass per pass does not result in a dryingtime that results in clogging of the nozzle during drying of depositedcoating material on the stent. In addition, the axial translation speedmay be increased so that the mass per pass results in a relativelyconsistent coating from pass to pass and that has an acceptable quantityand degree of defects.

Table 2 illustrates the effect of pump rate and linear or axial speed onthe mass per pass and coating quality. The coating quality was based ona visual inspection of the coated stent under a microscope. Inspectionsare performed of a coated stent at a magnification between 40× and 100×under a microscope. The coating quality is based on size and number ofdefects including the presence of cobwebs and rough spots. In general,in order to pass, a stent must be free of defects over a certain sizeand have less than a specified number of cobwebs and rough spots.

Coating runs were performed on a 28 mm stent for different pump rates ofcoating material and linear or axial speed of the stent under a nozzle.The mass per mass in each run was determined by the difference in weightof the stent before and after coating.

The coating runs included application of a primer layer and adrug-matrix or reservoir layer over the primer layer. The coatingmaterial for the primer layer was poly(n-butyl methacrylate) (PBMA) inan acetone/cyclohexanone solvent. The coating material for the reservoirlayer was poly(vinylidene fluoride-co-hexafluoropropene) copolymer(PVDF-HFP) (e.g., SOLEF 21508, available from Solvay Solexis PVDF,Thorofare, N.J.) in an acetone/cyclohexanone solvent.

The coating equipment included a Havard syringe pump obtained fromInstech Laboratories, Inc., Plymouth Meeting, Pa. The nozzle and mandrelused were developed in-house.

As shown in Table 2, Runs 1 and 2 were performed at a pump rate of 12mg/sec and linear or axial speed of 6 mm/sec. The mass per pass differedslightly between the two runs and the coating quality was a “pass.”

The linear or axial speed for Runs 3-6 was increased from 6 mm/sec to 12mm/sec from Runs 1 and 2. The pump rate for Runs 3-6 was the same asRuns 1 and 2. Table 2 shows, as expected, that the increase in thelinear or axial speed caused a decrease in the mass per mass. Asindicated above, an increase in linear or axial speed tends to decreasethe mass per pass. The mass per pass of Runs 3-6 is slightly more than athird of the mass per pass of Runs 1 and 2. In addition, the coatingquality was a “pass” for each of Runs 3-6.

In Runs 7-10, both the pump rate and linear or axial speed wereincreased over that used in Runs 3-6 from 12 ml/hr to 18 ml/hr and 12mm/sec to 18 mm/sec, respectively. In general, the increase in the pumprate tends to increase the mass per pass. However, the increase in thelinear or axial speed compensates for the increase in the increased pumprate since the mass per pass of Runs 7-10 is less than Runs 3-6. Thecoating quality is a “pass” for Runs 8-10 and a “fail” for Run 7.

In Runs 11 and 12, the pump rate and linear or axial speed were bothfurther increased over that used in Runs 7-10 from 18 ml/hr to 24 ml/hrand from 18 mm/sec to 24 mm/sec, respectively. In this case, theincrease in the pump rate resulted in an increase in the mass per pass.The increase in the linear or axial speed only partially compensated forthe increase in flow rate. In each of Runs 11 and 12, the coatingquality was a pass. Nominal refers to the center or standard parameterrun.

TABLE 2 Test coating runs for different pump rates and linear or axialspeed. Mass Per Pass Pump Rate Axial Speed Visual Test (μg/pass) (ml/hr)(mm/sec) Inspection Test Conditions for 28 mm Stent 1 92 12 6 Pass 2 9512 6 Pass 3 35 12 12 Pass 4 34 12 12 Pass 5 36 12 12 Pass 6 36 12 12Pass 7 24 18 18 Fail 8 23 18 18 Pass 9 23 18 18 Pass 10 19 18 18 Pass 1138 24 24 Pass 12 32 24 24 Pass Nominal Conditions for 28 mm Stent 13 305 6

Stent Support Assemblies

Another aspect of the present invention relates to reducing oreliminating coating defects that can result from stent contact withsupports, such as mandrels, during coating. A shortcoming of theabove-described method of medicating a stent through application of acoating is the potential for coating defects. While some coating defectscan be minimized by adjusting the coating parameters, other defectsoccur due to the nature of the interface between the stent and theapparatus on which the stent is supported during the coating process. Ahigh degree of surface contact between the stent and the supportingapparatus can provide regions in which the liquid composition can flow,wick, and collect as the composition is applied. As the solventevaporates, the excess composition hardens to form excess coating at andaround the contact points between the stent and the supportingapparatus. Upon the removal of the coated stent from the supportingapparatus, the excess coating may stick to the apparatus, therebyremoving some of the needed coating from the stent and leaving bareareas. Alternatively, the excess coating may stick to the stent, therebyleaving excess coating as clumps or pools on the struts or webbingbetween the struts.

Thus, it is desirable to minimize the influence of the interface betweenthe stent and the supporting apparatus during the coating process toreduce or coating defects. Accordingly, the present invention providesfor embodiments of a method and device for supporting a stent during thecoating application process that minimizes the influence of theinterface.

As described above, spray coating a stent typically involves mounting ordisposing a stent on a support, followed by spraying a coating materialfrom a nozzle onto the mounted stent. A stent can be supported, forexample, on a mandrel or rod that supports the stent along its length bypositioning the stent over the mandrel. A stent can also be supported atits ends with supports having a variety of geometries, such as taperedor untapered cylinders.

As indicated above, the interface or contact points between a stentsupport and the stent can lead to defects. This is particularly the casewhere the support and the stent do not move relative to one anotherduring the coating process. The lack of relative movement leads tostationary contact points between the stent and the support.

The contact area between a support and stent can be minimized by sizinga support such as a mandrel so that its diameter is less than the insidediameter of the stent. Similarly, the ends of a stent can be supportedloosely over tapered or untapered cylinders. Thus, as the mandrelrotates, the contact points continuously change. A disadvantage of thisapproach is that the stent can stick to the support members, resultingin stationary contact points.

Embodiments of the present invention relate to a method of and a devicefor shifting or changing the contact points of a stent with a supportduring a coating process. In certain embodiments, the shift in contactpoints may be accomplished by a pulse in the rotation rate of a supportmember that rotates and causes a stent to rotate. A “pulse” generallyrefers to a rise and/or fall in a quantity during a period of time.Shifting or changing a contact point, area, or interface refers to achange of a point, area, or interface of contact of a stent with asupport from one location of the support to another location of thesupport.

FIG. 9 depicts a mounting assembly 18 for supporting a stent 15including a rod or mandrel 20 and support elements 22. Mandrel 20 canconnect to a motor 24, which provides rotational motion to mandrel 20,as depicted by an arrow 26, during the coating process. Motor 24 is alsocapable of providing rotational pulses for shifting contact points, asdescribed below. Another motor 28 can also be provided for movingmandrel 20 and thus stent 15 in a linear or axial direction, back andforth, along a rail 30. Motor 28 is also capable of providingtranslational pulses to mandrel 20 along its axis. Pulsing motorsinclude an electronic gearing system that can cause a pulse or change inthe rotation rate or cause a pulse in the axial translation of a supportelement.

Mandrel 20 is illustrated as having two regions with a larger diameter.The two regions can be support elements 22 for applying a torque tostent 15. In commercially useful embodiments, any number of supportelements 22 can be used to adequately support stent 15. As shown,support elements 22 are sized larger than the outer diameter of mandrel20 so as to prevent mandrel 20 from being in contact with the innersurface of stent 15. Alternatively, in other embodiments, mandrel 20 canbe free of support elements 22 so that the stent is supported by and incontact with mandrel 20.

Additionally, support elements 22 are sized smaller than the innerdiameter of stent 15 so as to provide for minimum contact betweensupport elements 22 and the inner surface of stent 15. In the case of amandrel 20 free of support elements 22, mandrel 22 is sized smaller thanthe inner diameter of stent 15.

Support elements 22 of small diameter, as compared to the inner diameterof stent 10, results in an axis x_(M) about which support elements 22rotate, that is offset from an axis x_(S), about which stent 15 rotates.Axis x_(S) is positioned longitudinally through the center of stent 15.Since support elements 22 and stent 15 rotate about different axes,x_(M) and x_(S), support elements 22 and stent 15 do not have a 1:1rotation. Thus, the contact points or area between support 22 and stent15 continuously change. However, coating material can cause stent 15 tostick to support elements 22, resulting in a stationary contact point.

Sticking of stent 15 to support elements 22 is reduced or prevented bypulsing the rotation rate of mandrel 20 and elements 22. The pulses inrotation rate cause a stent that is stuck to one or both of supportelements 22 to break free and resume rotation about axis x_(S) withcontinuously changing contact points.

Numerous variations of the form of a pulse that could break a stent freeare possible. FIGS. 10A-D each depict the rotation rate as a function oftime for representative pulses. The pulse duration can be, for example,between 0.0001 sec and 1 sec. A pulse duration outside this range can becontemplated by one of skill in the art. R₁ is the rate prior to thepulse, R₂ is the maximum rate of the pulse, and R₃ is a final rate ofthe pulse (in FIGS. 10A-C). R₁ can also correspond to the rotation rateof the opposing non-pulsing element. FIGS. 10A-D depict pulses that havean increase in rotation rate. However, pulses with a decrease inrotation rate can also be used to reduce or prevent sticking, as well asshifting contact points, as described below.

In FIGS. 10A-C, the rotation rate increases from R₁ to a peak at R₂ andthen decreases to R₃. R₃ is greater than R₁ in FIG. 10A, less than R₁ inFIG. 10B, and the same as R₁ in FIG. 10C. The maximum rate, R₂ of thepulse can be greater than 10%, 30%, 60%, 80%, or more narrowly greaterthan 100% of the rate prior to the pulse, R₁.

The pulses can be performed at a specified frequency during the coatingprocess to reduce or eliminate sticking of the stent that can occur. Thefrequency can be greater than 0.1 Hz, 0.5 Hz, 1 Hz, 3 Hz, or morenarrowly 5 Hz. Alternatively, the pulses can be performed at irregularor unequal intervals.

A pulse causes a rotation of elements 22 relative to stent 15. Therelative rotation caused by an increase in rate from R₁ to R₂ can begreater than 10°, 30°, 45°, 90°, or 270°. The amount of rotation can becontrolled by the maximum rate of the pulse, the degree of acceleration,and the duration of the pulse. It is believed that the higher rate R₂ ordegree of acceleration, the greater is the relative rotation of elements22 to stent 15.

FIG. 11A depicts a mounting assembly 40 which supports stent 45 viasupport elements 42 and 44. Support elements 42 and 44 have acylindrical cross-section and taper inwardly toward stent 45. As shown,the ends of stent 45 can rest on the tapered portions of supportelements 42 and 44. A variety of shapes can be contemplated by one ofordinary skill in the art for support elements 42 and 44.

Support elements 42 and 44 can connect to motors 46 and 48,respectively, which provide rotational motion to support elements 42 and44, as depicted by arrows 50 and 52, during the coating process. Motors46 and 48 are also capable of providing rotational pulses for shiftingcontact points, as described below. Motors 54 and 56 can also beprovided for providing pulses to support elements 42 and 44 in a lineardirection along rails 58 and 60, respectively. Motors 54 and 56 are alsoused to position support elements 42 and 44 relative to one another.Another motor (not shown) can also be provided to move assembly 40 andthus stent 45 in a linear direction, back and forth, during coating.

Support elements 42 and 44 can be positioned by motors 54 and 56,respectively, so that support elements 42 and 44 and stent 45 have thesame or substantially the same axes of rotation. Opposing forces exertedfrom support elements 42 and 44, for securely pinching stent 45 againstsupport elements 42 and 44, should be sufficiently strong so as toprevent any significant movement of stent 45 on mounting assembly 40.The forces can be sufficiently strong so that there is a 1:1 rotation ofstent 45 with support elements 42 and 44.

However, the exerted force should not compress stent 45 so as to distortthe body of stent 45. Over or under application of support force canlead to problems such as stent 45 resting too loosely on mountingassembly 20, stent 45 bending, opposing ends of stent 45 flaring onsupport elements 42 and 44, and increased contact between stent 10 andsupport elements 42 and 44, all of which can lead to coating defects.

Additionally, stent 45 can be disposed loose enough on support elements42 or 44 so that there is not 1:1 rotation between stent 45 and supportelements 42 or 44. Support elements 42 and 44 can be positioned relativeto one another so that stent 45 has an axis of rotation different froman axis of rotation of the support elements. In this case, the contactpoints or area between support elements 42 and 44 and stent 10continuously change.

When there is 1:1 rotation between a support element and the stent,contact points between the support and the stent tend not to change ifthe rotation rate of elements 42 and 44 are the same. As discussedabove, contact points that do not change for all or a substantial partof the coating process can lead to coating defects. A shift in contactpoints during coating can reduce or eliminate defects due to contactpoints during coating. Providing a rotational pulse to a support elementcan shift the contact points between the support element and the stent.Contact points that are uncovered due to a shift may then be covered bycoating material. A repeated shifting of contact points during coatingtends to allow coating material to cover defects or uncoated regionscaused by contact points during the coating process.

Motor 46 can rotate support element 42 at the same or different rate asmotor 48 rotates support element 44. Thus, motor 46 and motor 48 canprovide rotational pulses independent of one another to support elements42 and 44, respectively, to shift contact points between stent 45 andsupport elements 42 and 44. The pulses can take the form of those shownin FIGS. 10A-D. As discussed above, a rotational pulse causes a rotationof support elements 42 or 44 relative to stent 45. An increase inrotation rate of element 42 from R₁ to R₂ causes element 42 to rotateahead of stent 302 resulting in a shift of contact points between stent45 and element 42. The relative rotation can continue as long therotation rate of element 42 differs from element 44. However, if bothends of the stent are stuck, coupled, or attached to the respectivecollets resulting in 1:1 rotation at each end, a difference in velocitybetween the ends could damage or destroy the stent. The stent could betwisted and damaged or destroyed by a torsional force.

The pulses can be performed at a specified frequency during the coatingto reduce or eliminate the defects caused by contact points. A pulserotates elements 42 or 44 relative to stent 45 resulting in differentcontact points after the pulse. As above, the relative rotation can begreater than 10°, 30°, 45°, 90°, or 270°. The degree of rotation can becontrolled by the maximum rate of the pulse, the degree of acceleration,and the duration of the pulse.

When stent 45 is loosely supported on support elements 42 and 44 so thatthere is not a 1:1 rotation, rotational pulses can reduce or preventsticking of stent 45 to support elements 42. Sticking can also bereduced or prevented by rotating support elements 42 and 44 at differentrates. Rotating support elements 42 and 44 at different rates can reduceor prevent sticking of the ends of stent 10 to elements 42 or 44. Thedifference in torque at the different ends of stent 10 causes the slowerend to pull back on the faster end and the faster end to pull forward onthe slower end to reduce or prevent sticking or to break free an endthat is sticking. The difference in torque between elements 42 and 44should be small enough so as not to cause excessive flexure to thestent.

Contact points between stent 45 and support elements 42 and 44 can beshifted by pulsing support elements 42 and 44 in a linear direction.Sticking of stent 45 to support elements 42 or 44 can also be reduced orprevented by linear pulses. Motor 54 or motor 56 can provide linearpulses independent of one another to support elements 42 and 44,respectively. A linear pulse involves an axial translation of supportelements 42 or 44 by motors 54 or 56, respectively.

Motors 54 or 56 can pulse support elements 42 or 44, respectively,either inward toward stent 45 or outward away from stent 45. Arepresentative linear pulse showing linear translation rate versus timeis depicted in FIG. 12. The rate corresponds to the linear translationrate of support element 42 or 44 relative to the assembly 40 which canbe translated back a forth during coating. In FIG. 12, the translationrate increases from zero to R_(max) and then returns to zero. Forexample, support element 42 can be pulsed inward toward stent 45 with apulse having the functional form in FIG. 12. Support element 42 can bepulsed outward in a similar manner.

Pulses or a suitable combination of pulses can cause axial translationof supports 42 and 44 with respect to stent 45 in a number of ways.FIGS. 13A-H show the axial position of an end of support element 42 or44 as a function of time. “x₁” is the initial position of a point on asupport element, “x₂” is the maximum linear deviation from the initialposition. “x₃” is the final position of the support element in FIGS.13C-H. FIGS. 13A-B depict movement of a support element from a positionx₁ to a position x₂. For example, for support element 42, FIG. 13Adepicts a movement inward and 13B is a movement outward from the stent.FIGS. 13C-D depict a movement of a support element from a position x₁ toa position x₂ followed by a movement back to x₁. FIGS. 13E-F depict amovement of a support element from a position x₁ to a position x₂followed by a movement to a position between x₁ and x₂. FIGS. 13G-Hdepict a movement from of a support element from a position x₁ to aposition x₂ followed by a movement to a position that is further from x₂than x₁.

The linear pulses tend to reduce or prevent sticking of the stent tosupport element 42 or 44. When support element 42 or 44 is translatedinward toward the stent, the stent tends to slide or ride upward alongthe upper tapered portion of support element 42 or 43. Similarly, whensupport element 42 or 44 is translated outward away from the stent, thestent tends to slide or ride downward along the upper tapered portion ofsupport element 42 or 44.

FIG. 11B depicts a part of a mounting assembly with support elements 62and 64 supporting stent 55. Support elements 62 and 64 are untaperedcylindrical elements. Support elements 62 and 64 can be sized so thatthere is a 1:1 rotation between stent 55 and the support elements.Rotational and linear pulses can be used to shift contact points betweensupport elements 62 and 64 and stent 55. Support elements 62 and 64 canbe sized smaller than the inner diameter of stent 55 so that the supportelements and stent 55 have a different axis of rotation. Sticking ofstent 55 to support elements 62 and 64 can be reduced or prevented byrotational and linear pulses.

In further embodiments, assembly 40 can include only one rotatablesupport element, e.g., support element 42, with the opposing supportelement being rotationally fixed. An end of stent 45 can fit looselyover an opposing support element so that there is not a 1:1 rotation ofstent 45 with the support element. Such a support element can have avariety of shapes including those pictured in FIGS. 11A-B.

FIGS. 14A-B depict an additional exemplary embodiment of a stent supportassembly 300 that provides for changing or shifting of contact points ofa stent 302 with a stent support. Stent 302 has a geometry composed of aplurality of undulating and intersecting elements or struts 302A.Assembly 300 includes a rotary spindle 304 and a rotary spindle 306 thatcan rotate independently of one another.

A support element 308 and a support element 310 are coupled to rotaryspindle 304 and rotary spindle 306, respectively. Rotary spindles 304and 306 can rotate support elements 308 and 310, and thus, stent 302supported by elements 308 and 310. Support element 308 supports aproximal end 309 of stent 302 and support 310 supports a distal end 311of stent 302. Rotary spindles 304 and 306 are each connected to motors(not shown) which provide rotational motion to support elements 308 and310 and to stent 302. The rotational motors are also capable ofproviding rotational pulses, as described above. Additionally, rotaryspindles 304 and 306 are also connected to linear motors (not shown) forpositioning support elements 308 and 310 relative to one another and forproviding translational pulses to support elements 308 and 310 in alinear or axial direction. Another motor (not shown) can also beprovided to move an assembly including spindles 304 and 306, and thus,stent 302 in a linear direction, back and forth, during coating.

Support element 308 includes three elongate arms 312 coupled to spindle304 and support element 310 also includes three elongate arms 314coupled to spindle 306. Elongate arms 312 and 314 converge inwardly toform a conical or frusto-conical shape for supporting stent 302. Asdepicted in FIG. 14B, elements 312 and 314 have cylindricalcross-sections and have pointed ends 318 that taper to a thin tip.Elements 312 and 314 can have other cross-sectional shapes such astriangular, square, rectangular, etc. Also, ends 318 can be flat orrounded. Elongate arms 312 and 314 may be, for example, wires or rods.

The ends of spindles 304 and 306 each have projecting portions 305 and307. Portion 307 has an inner edge 307A, an edge 307B that tapers inwardtoward stent 302 to meet edge 307A, an edge 307C that tapers outwardtoward stent 302 to meet edge 307B. An edge 307D tapers inward towardstent 302 to meet edge 307C. Spindle 304 has corresponding elementsincluding edge 305B, edge 305C, and edge 305D. Edge 307D has a longer amore gradual taper than edge 305D.

As shown in FIG. 14B, elongate arms 312 and 314 are coupled to rotationspindles 304 and 306. Edges 307A and 307C have holes sized to receiveelements 314. Elements 314 are disposed through the holes to coupleelements 314 to portion 307. Elements 312 are similarly coupled to ordisposed in portion 305. Elongate arms 312 and 314 can be, for example,screwed, glued, riveted, or friction-fitted into the holes.

Elongate arms 312 and 314 extend into and support a proximal end 309 anda distal end 311, respectively of stent 302. Each of elongate arms 312and 314 have at least one point or area of contact with struts 302A atproximal end 309 and distal end 311, respectively. Elongate arms 312 and314 are sized to be capable of supporting the stent, for example, sothat an elongate arm can support stent 302 without passing through anarrow portion 303 of the stent pattern. Support elements 308 and 310are positioned within ends 309 and 311 by translating the supportelements with respect to each other using the linear motors mentionedabove.

In one embodiment, elongate elements 312 and 314 can be rigid such thatthe elements exhibit no or relatively no bending while being positionedwithin a stent or during coating. Alternatively, elongate elements 312or 314 can be flexible. As flexible elements 312 or 314 are positionedinto an end of stent 302, the flexible elements bend inward and canexhibit an outward radial force that facilitates securing the elongateelements to stent 302.

Stent 302 can be rotated during coating by rotating rotary spindles 304and 306 which rotate support elements 308 and 310, and thus, stent 302.Elements 308 and 310 can be positioned within ends 309 and 311 so thatthere is 1:1 rotation between elements 308 and 310 and stent 302. Asdescribed for elements 42 and 44 in FIG. 11A, the relative distancebetween elements 308 and 310 can be decreased so that elongate elements312 and 314 securely pinch ends 309 and 311 of stent 302. The opposingforces exerted from support elements 308 and 310 should be sufficientlystrong so as to prevent any significant movement of stent 302. However,the exerted force should not compress stent 302 so as to distort thebody of stent 302. When support elements 308 and 310 rotate at the samerate or rotate in phase, the contact points between elements 308 and 310with stent 302 tend to remain the same, as described for elements 42 or44 in FIG. 11A.

Providing a rotational pulse to, for example, element 308 causes a shiftor change in the contact points between each of elements 312 and stent302. Referring to FIG. 10A-D, an increase in rotation rate of element308 from R₁ to R₂ causes element 308 to rotate ahead of stent 302resulting in a shift of contact points between stent 302 and element308. The relative rotation can continue as long the rotation rate ofelement 308 differs from element 310. The degree of relative rotationwould depend on the length of the stent and the torsional stiffness ofthe stent in order to cause separation of the support elements.

For example, for a pulse represented by FIG. 10A, the final rotationrate R₃ is greater than R₁ which causes element 308 to continue torotate ahead of or faster than stent 302. The final rotation rate mustbe the same for both spindles if the stent is keyed into element 308 for1:1 rotation, otherwise the stent can be damaged through torsion.Similarly, for the pulse of FIG. 10D, element 308 continues to rotateahead of or faster than stent 302 as long as the rotation rate is at R₂.For a pulse shown by FIG. 10B, the final rotation rate is less than R₁which causes element 308 to rotate behind or slower than stent 302. Thefinal rotation rate, R₃, is the same as the pre-pulse rotation rate, R₁,in FIG. 10C. Thus, element 308 stops rotating relative to stent 302 whenthe rotation rate of element 308 returns to R₃. After the pulse, element308 has different contact points with stent 302.

As described above, pulses can be performed at a specified frequencyresulting in a change in contact points at the specified frequency.Alternatively, pulses can be performed at irregular intervals.

Similar to the embodiment in FIG. 11A, contact points between stent 302and elements 308 and 310 can be shifted by pulsing element 308 or 310 ina linear direction. The linear motors can provide linear pulses toelements 308 or 310. As above, a linear pulse is an axial translation ofelement 308 or 310.

The linear pulses tend to reduce or prevent sticking of the stent toelongate elements 312 or 314. Translation of support element 308, forexample, inward toward stent 302 causes struts 302A of stent 302 toslide or ride upward along elements 312. Similarly, translation ofsupport element 308 outward from the stent, causes struts 302A to slideor ride downward along elements 312. A representative linear pulse isshown in FIG. 12. The rate corresponds to the linear translation rate ofsupport element 308 or 310 relative to an assembly that includes system300 which translates back a forth during coating. For example, supportmember 308 can be pulsed inward toward stent 302 with a pulse having thefunctional form in FIG. 12. Support element 308 can be pulsed outward ina similar manner.

Pulses or a suitable combination of pulses can cause axial translationof supports 308 and 310 with respect to stent 302 in a number of ways.As described above, FIGS. 13A-H show the axial position of an end ofsupport element 308 or 310 as a function of time.

Furthermore, translational pulses of elements 308 or 310 can beperformed at a specified frequency resulting in a change in contactpoints at the specified frequency. Alternatively, pulses can beperformed at irregular intervals.

In other embodiments, assembly 300 can include an element disposedaxially within stent 302 at least between support element 308 andsupport element 310. Alternatively, the member may extend betweenspindle 304 and spindle 306. The member may include, but is not limitedto, a rod or wire. The member may be coupled to the support members ateach end in a manner than allows independent rotation of the rotaryspindles.

In additional embodiments, assembly 300 can include only one rotatablesupport element, e.g., support element 308, with an opposing supportelement being rotationally fixed. Distal end 311 of stent 302 can fitloosely over an opposing support element so that there is not a 1:1rotation of stent 302 with the support element. Such a support elementcan have a variety of shapes including those pictured in FIGS. 11A-B andFIGS. 14A-B.

A further aspect of the present invention relates to eliminating coatingdefects that can result from stent contact with supports, such asmandrels, during coating. Additional embodiments of the presentinvention involve selectively coating portions of a stent that have nocontact points.

FIGS. 15A-B depict views of an exemplary embodiment of a stent supportassembly 400 for coating a stent 402 having a proximal end 402A and adistal end 402B. FIG. 15A depicts a side view of assembly 400 and FIG.15B depicts an axial cross-section of assembly 400. As described below,assembly 400 is configured to selectively coat portions of stent 402that have no contact points. An exemplary stent 402 has a geometrycomposed of a plurality of undulating and intersecting elements orstruts 403.

As shown in FIG. 15B, assembly 400 includes a rotation spindle 404 and arotation spindle 406 that can rotate independently of one another. Asupport mandrel 408 is coupled to rotation spindle 404 at a proximal end409A of mandrel 408 as shown. A distal end 409B of mandrel 408 is freefloating, i.e., not coupled or connected to another support element. Asupport mandrel 410 is coupled to rotation spindle 406 at a proximal end411A of mandrel 410. A distal end 411B is free floating. Thus, distalend 409B of support mandrel 408 and distal end 411B of support mandrel410 are separated by a gap 413. As described above, gap 413 isadjustable.

A masking sheath 420 is disposed over spindle 404 and can be translatedaxially over rotation spindle 404. A shuttle sheath 430 is positionedover support mandrel 408 which can axially translate over supportmandrel 408. In a similar manner, shuttle sheath 421 is disposed overspindle 406 and shuttle sheath 431 is disposed over support mandrel 410.

Either or both rotation spindle 404 and rotation spindle 406 can beaxially translated as shown by arrows 414 and 415, respectively. Priorto coating, stent 402 is loaded onto support mandrel 408 by slidingstent 402 onto support mandrel 408. Alternatively, stent 402 can also beloaded onto support mandrel 410. Prior to loading stent 402 on supportmandrel 408, one or both of the rotation spindles can be axiallytranslated to their maximum separation position or at least to aposition that allows loading of stent 402.

As shown in FIGS. 15A-B, stent 402 is loaded so that a portion 416 ofstent 402 is over support mandrel 408 and a portion 418 extends beyonddistal end 409B of support mandrel 408. Portion 418 is free of contactpoints with support mandrel 408 and any other support element. Portion416 can be long enough so that there is adequate support for portion418, for example, so that there is no or substantially no sagging ofportion 418. It is expected that the longer the stent, a largerpercentage of the length of stent 402 should be over mandrel support408. For example, portion 416 can be less than 30%, 40%, 50%, 60%, or70% of the length of stent 402. It may be desirable for portion 418 tobe as large as possible since, as described below, a coating material isapplied to a majority of portion 418.

FIGS. 16A-B depict views of assembly 400 showing masking sheath 420translated axially from rotation spindle 420, as shown by an arrow 422,to mask or cover at least portion 416 of stent 402 in FIG. 15A. FIG. 16Adepicts a side view of assembly 400 and FIG. 16B depicts an axialcross-section of one side of assembly 400. As shown, a portion 424 isunmasked. Preferably sheath 420 masks portion 416 and a small axialsection of portion 418 to inhibit or prevent exposure of portion 416 tocoating material. For example, the small axial section may be less than1%, 3%, 5%, 8%, 10%, or less than 15% of a length of stent 402.

After positioning masking sheath 420, a coating material 425 is appliedto unmasked portion 424 from a spray nozzle 427 positioned above stent402. Stent 402 is rotated by rotation spindle 404, as shown by an arrow426 during coating. Additionally, stent 402 is axially translated byaxially translating rotation spindle 404 along with masking sheath 420,as shown by an arrow 428, during coating. Alternatively or additionally,spray nozzle 427 can be translated along unmasked portion 424.

At least one pass of spray nozzle 427 from one end of portion 424 to theother can be made over stent 402. After a desired amount of coatingmaterial is applied to unmasked portion 424, the coating applied onstent 402 is dried according to methods known to a person of skill inthe art or by methods disclosed herein. Stent 402 can be dried at thesame location as it is sprayed or moved to a drying station (not shown).Alternatively, the coating can be dried at the same time it is beingsprayed. The spraying-drying cycle can be repeated a number of timesuntil a desired amount of coating material has been applied to thestent.

To coat the masked portion of stent 402, stent 402 is loaded ontosupport mandrel 410 by axially translating support mandrel 408 towardsupport mandrel 410, decreasing adjustable gap 413 shown in FIGS. 15A-B.Mandrel 408 is axially translated so that distal end 402B of stent 402engages distal end 411B of mandrel 410. Distal end 411B is tapered tofacilitate engagement of stent 402 on distal end 411B.

FIG. 17A depicts a side view of assembly 400 showing shuttle sheath 430positioned over support mandrel 408 axially translated towards supportmandrel 410 as shown by an arrow 432. FIG. 17B depicts an axialcross-section of one side of assembly 400 showing shuttle sheath 430over support mandrel 408. As shuttle sheath 430 translates, it pushesagainst stent 402 at proximal end 402A so that stent 402 is pushed offsupport mandrel 408 and onto support mandrel 410.

As shown in FIG. 17A, stent 402 is positioned on support mandrel 410 ina manner that is similar to support mandrel 408. In particular, stent402 is loaded on support mandrel 410 so that a portion 436 of the stentis over support mandrel 410 and a portion 438 extends beyond distal end411B of support mandrel 410. Portion 438 is free of contact points withsupport mandrel 410 and any other support element. Portion 436 can belong enough so that there is adequate support for portion 438, forexample, so that there is no or substantially no sagging of portion 438.Portion 438 includes at least the portion of stent 402 that was notcoated while stent 402 was loaded on mandrel support 408.

In a manner similar to that described above, a masking sheath translatesaxially from rotation spindle 406 to mask or cover portion 436. Afterpositioning the masking sheath, coating material 425 is applied to theunmasked portion from spray nozzle 427 positioned above stent 402. Stent402 is rotated by rotation spindle 406 during coating. Additionally,stent 402 is axially translated by axially translating rotation spindle406 during coating. Alternatively or additionally, spray nozzle 427 canbe translated along an axis of the unmasked portion. At least one passof spray nozzle 427 can be made over stent 402. After a desired amountof coating material is applied to the unmasked portion, the coatingapplied on stent 402 is dried. The spraying-drying cycle can be repeateda number of times until a desired amount of coating material has beenapplied to the stent.

After coating stent 402 on support mandrel 410, stent 402 is loaded backonto support mandrel 408 if it is desired to apply additional coating toportion 418. Stent 402 may be loaded back onto support mandrel 410 in asimilar manner as the transfer of stent 402 from support mandrel 408 tosupport mandrel 410. For example, either or both of the support mandrelscan be axially translated toward one another so that proximal end 402Aof stent 402 engages distal end 409B of mandrel 408. Distal end 409B istapered to facilitate engagement of stent 402 on distal end 409B. Ashuttle sheath positioned over support mandrel 408 can push againststent 402 at proximal end 402B so that stent 402 is pushed off supportmandrel 410 and onto support mandrel 408. The sequence of stepsdescribed above involving coating on support mandrel 408, drying thecoated portion, transferring stent 402 to support mandrel 410, coatingstent 402 on support mandrel 410, can be repeated a selected number oftimes until a specified loading of coating is applied to stent 402.

In some embodiments, support mandrels 408 and 410 could be covered,coated, or jacketed with a lubricious material, such as Teflon, toreduce or eliminate defects that could be caused by interaction of theinside diameter (ID) of stent 402 with the outside surface of themandrels. Additionally, in one embodiment, the outside diameter of themandrels can be sized to allow a slip or friction-fit so that there is a1:1 rotation of stent 402 with the mandrels.

In alternative embodiments, stent 402 can be coated by sequential spraycoating of any number of contactless portions of stent 402. For example,stent 402 can be disposed so that a proximal portion is over supportmandrel 408 and a distal portion is over support mandrel 410 with acenter portion having no contact with either mandrel. FIG. 18 depicts anembodiment for coating a central portion 440 of stent 402. Proximal anddistal portions (not shown) of stent 402 are masked by masking sheaths442 and 444. Masking sheaths 442 and 444 are disposed over proximal anddistal portions of stent 402 after disposing the proximal and distalportions over support mandrel 408 and support mandrel 410, respectively.

Additional aspects of the present invention relate to devices andmethods for supporting a stent during coating, processing, or handlingthat reduce or eliminate defects in the stent coating. Variousembodiments include a system for supporting a stent having supportmembers that contact proximal and distal portions of a stent that areconnected with a connecting member that extends between the supportmembers outside of and free of any contact with the stent.

FIG. 19A depicts a three-dimensional view of an exemplary embodiment ofa stent support assembly 500. Support 500 includes pins or rods 502 and504 which are coupled to collets 506 and 508, respectively. Collets 506and 508 are coupled to a proximal and a distal end of a support bar 512,respectively. A stent can be supported on pins 502 and 504 betweencollets 506 and 508.

FIG. 19B depicts a close-up side view of a proximal end 505 of support500. As depicted in FIG. 19B, pin 502 can be embedded in one side ofcollet 506 and rod 510 can be embedded in an opposite side of collet506. Pin 504 and rod 511 can be coupled to collet 508 in a similarmanner. Rod 511 extends through a distal end of support bar 512 and rod510 extends through a proximal end of support bar 512. As shown in FIGS.19A and 19B, rod 510 and rod 511 can have a larger diameter on the sideopposite of collets 506 and 508, respectively. In other embodiments, rod510 and rod 511 have the same diameter on both sides of collets 506 and508, respectively.

FIGS. 19A and 20 show that support bar 512 is shaped in the form of a“C-clamp.” Support bar 512 is designed so that it may be held, grasped,or manipulated during and/or before processing of a stent. Thus, othershapes of support bar 512 may be contemplated that allow supportassembly 500 to be grasped, handled, or manipulated by a human hand ormechanically without contacting or interfering with a mounted stent. Forexample, support bar 512 can also be U-shaped.

In the exemplary embodiment depicted in FIG. 19A, pin 504, along withcollet 508 and rod 511, are rotationally and axially fixed about andalong axis 516. Pin 502, along with collet 506 and rod 510 arerotationally and axially movable about and along axis 518. As shown, rod510 has a spring 520 that allows pin 502 to be retracted axially, asshown by an arrow 522, a specified distance. The retracted pin is thenreturned to and held at its original position by the force of spring520. Retracting pin 502 allows a stent to be mounted or a mounted stentto be removed from support assembly 500. Pin 502 can be retracted bypulling rod 510 as shown by an arrow 523. Releasing rod 510 then allowspin 502 to return to its original position.

When pin 502 is retracted, a stent can be mounted by inserting aproximal end of a stent over pin 502 and a distal end of a stent overpin 504. Pin 502 is then pushed forward by the force of spring 520 tosecure the stent on pins 502 and 504. Similarly, a mounted stent can beremoved when pin 502 is retracted. The ability to load and unload astent on a support with contact points limited pins 502 and 504, reducesor eliminates the potential for defects due to handling or manipulationof the stent.

FIG. 20 depicts a side view of an exemplary embodiment of supportassembly 500. Representative dimensions are provided for supportassembly 500. All dimensions are in centimeters. The representativedimensions are provided by way of example only and in no way areintended to limit support assembly 500.

FIG. 21 depicts a stent 532 mounted on support assembly 500. Stent 532can be rotated by support 500, for example, during application of acoating to the stent. Rod 510 is coupled or engaged in a chuck in arotatable spindle 525 that is coupled to a stationary support 526.Rotatable spindle 525 rotates rod 510 as shown by an arrow 528 whichrotates rod 510 and collet 506 as shown by arrows 530.

A stent 532 can be mounted such that a length of stent 532 is less thana distance between collets 506 and 508 such that the stent can move fromside to side during rotation. In another embodiment, a proximal end 534and distal end 536 of stent 532 are at least partially in contact with asurface of collets 506 and 508, respectively. Collet 506 and pin 502 arepositioned axially to contact stent 532 to allow a 1:1 rotation ofcollet 506 and stent 532. Collet 506 can have a protrusion or pin 538,as shown in FIG. 19A, positioned on its surface to reduce or preventsticking of proximal end 534 to collet 506 during rotation. Protrusion538 can make contact with a proximal end 534 that is sticking to collet506, causing it break free.

In addition to use as a support during coating, support assembly 500 canbe used as a support during various portions of stent processing.Support assembly 500 can be used generally for handling or manipulatinga stent between and during processing steps. Support 500 can be used inoperations such as weighing, inspection, and transport. When weighing astent, the support bar can be held by hand and the spring-loaded end-pincan be grasped by the other hand.

For example, a coated stent 532 that is to be weighed can be loaded on aweigh pan by holding stent 532 over the weigh pan, retractingspring-loaded pin 502 and allowing coated stent 532 to be placed ontothe weigh pan. Retracted pin 502 is allowed to return to a relaxedposition. Thus, stent 532 may be loaded on the weigh pan without anyadditional contact of stent 532 with support 500. When the stentweighing process (or any other process) is complete, spring-loaded pin502 can be retracted again to allow enough space for fixed pin 504 to beplaced into distal end 536 of stent 532. Spring-loaded pin 502 can thenbe inserted into proximal end 534 of stent 532 to secure stent 532 ontosupport 500 for further transport, handling, or processing.

Further aspects of the present invention relate to devices and methodsfor supporting a stent during coating, processing, or handling thatreduce or eliminate defects in the stent coating. Various embodimentsinclude a system for supporting a stent with reduced contact points of asupport with a stent. The stent support includes a spiral coil or spiralmandrel that can be disposed within a stent to support the stent duringcoating.

FIGS. 22A and 22B depict exemplary embodiments of spiral coil supportsfor supporting a stent. FIG. 22A depicts a two-dimensional view of aspiral coil support 550 having a coiled portion 552, two straightportions 556 and 557 on either side of coiled portion 552. Peaks 558 ofcoiled portion 552 provide contact points with an inner surface of astent to support the stent. An outside diameter 564 of coiled portion552 from a peak 558 to a valley 560 is sized to be smaller than aninside diameter of a stent. Thus, as support 550 rotates the contactpoints alternate along the coil. Alternatively, diameter 564 is sized toobtain a friction fit or press fit between an inner surface of the stentand coiled portion 552. A “pitch” of a spiral coil refers to a distancefrom any point on the coil to a corresponding point on the coil measuredparallel to the axis of the coil. For example, spiral coil support 550has a pitch 562.

FIG. 22B depicts an illustration of a prototype of a spiral coil supporthaving a pitch 568. The spiral coil is made from wire with a 0.017 inchoutside diameter.

An advantage of a support as depicted in FIGS. 22A and 22B is that thenumber of contact points with a stent may be controlled by controllingpitch 562 of coiled portion 552. Increasing pitch 562 reduces the numberof contact points of coiled portion 552 with a supported stent. However,the support provided to the stent is reduced by increasing the pitch. Inone embodiment, a coil with a pitch of less than three, less than four,less than five, less than six, or more narrowly, less than seven pitchper inch may be used for coating a 28 mm stent. In an embodiment, thepitch may be controlled so that the total contact points may be lessthan three, less than four, less than five, or more narrowly less thanseven.

An example of a spiral coil support 550 depicted in FIG. 22A hasdimensions as follows: Length of straight portion 556=0.15 inch, Lengthof straight portion 557=1.05 inch, Length of coiled portion 552=2 inch,Diameter 564=0.05±0.005 inch, and Pitch 562=0.2 inch.

FIG. 23A depicts a holder 570 for a spiral coil support for manipulatingand positioning a spiral coil support. Holder 570 has a cylindricalcross-section. In an embodiment, holder 570 may be used to manipulateand position a spiral coil support before and after coating. Holder 570can also support a spiral coil support during coating. Holder 570includes a proximal tapered section 572 having a cavity or hole 574.Cavity 574 is capable of receiving a straight portion 556 or 557 of aspiral coil support. Straight portion 556 or 557 of a spiral coilsupport can be coupled within hole 574 by a press fit and/or by gluing.Straight portion 556 or 557 and hole 574 can also be threaded for ascrew fit.

FIG. 23B depicts a radial cross-section of the front of tapered section572. A middle section 576 has a larger diameter than a distal section578. Distal section 578 can be sized and adapted to engage into arotatable spindle for rotating holder 570 during coating. For example,distal section 578 includes a tapered portion 578A for adapting to asupport structure or rotatable spindle. An example of holder 570depicted in FIGS. 22A-B has dimensions as follows: L₁=1.65 inch, L₂=1.2,L₃=0.45, L₄=0.125 inch, L₅=0.051, D₁=0.0995 to 0.1 inch, D₂=0.017 to0.0175 inch, D₃=0.125 inch, θ₁=45°, and θ₂=45°.

FIG. 24A depicts a picture of a spiral coil support 580 supported by aholder 582. Holder 582 is used to position support 580, as shown by anarrow 586, within a stent 584 to be coated. FIG. 24B depicts a close-upview of support 580 disposed within stent 584. When holder 582 iscoupled with a rotating spindle, it can rotate support 580 and stent 584as shown by an arrow 588.

FIG. 25 depicts an axial view of an assembly 590 for coating a stent 592supported by spiral coil support 594. The coiled portion of spiral coilsupport 594 supports stent 592 at contact points 596. Straight portion598 of spiral coil support 594 is coupled to a holder 600 like thatshown in FIG. 23A. Holder 600 can rotate as shown by an arrow 602 whichrotates support 594 and stent 592. A straight portion 604 can be coupledto a fixed or rotatable spindle or member 606. Assembly 590 can alsoaxially translate stent 592 relative to a nozzle spraying coatingmaterial onto stent 592.

FIGS. 26A-D depict scanning electron micrograph (SEM) images of 28 mmstents coated using an embodiment of a spiral coil support or spiralmandrel. The stent used in the examples are Xience V medium stentobtained from Guidant Corporation in Santa Clara, Calif. The pump rateof coating material during spraying of the stent was 3 ml/hr and therotation rate of the stent was 100 rpm. The drying nozzle was set to 55°C. at an air pressure of 20 psi. FIG. 26A depicts an outside surface ofa coated stent. FIG. 26B depicts an end ring of a coated stent. FIG. 26Cdepicts a close-up view of an outside surface of a coated stent. FIG.26D depicts a close-up view of an inside surface of a coated stent.

Another aspect of the present invention relates to a device that allowsreduced contact area between a support for a stent and the ends of astent during coating of the stent. FIG. 27 depicts a side view of astent support assembly 700 including a mandrel 702 and support collets704 for supporting a stent. Assembly 700 also includes collets 706 forsecuring a stent mounted over a mandrel in an axial direction. One orboth of members 708 can be rotatable spindles for rotating mandrel 702which rotates a stent mounted on mandrel 702. At least one of members708 can be rotationally and axially fixed.

As indicated above, it is generally desirable to minimize the contactarea between an end of a stent and collets 706 to reduce or preventcoating defects. Additionally, minimizing such contact area tends toreduce undesirable wicking or flow of coating material from the stent tothe collets. Contact points can create defects such as uncoated orinsufficiently coated areas on a stent surface. Wicking can also resultin uncoated or insufficiently coated areas.

It is desirable to minimize the interface between the end of a stent andthe apparatus supporting the stent end during the coating process tominimize coating defects. Accordingly, the present invention providesfor a device for supporting a stent during the coating applicationprocess. The invention also provides for a method of coating the stentsupported by the device.

Various embodiments of the present invention include a collet that isshaped so as to minimize contact area of a stent end with a surface ofthe collet. Certain embodiments of the collet have an end surface forcontacting a stent end that includes a raised or projecting portion anda flat or relatively flat portion. In one embodiment, the projectingportion may have at least three segments radiating from a center to theedge of the surface. The thickness of the segments in a plane of thesurface may decrease from the center to the edge of the surface.Additionally, a height of the projecting portion perpendicular to thesurface may decrease from the center of the surface to the edge.

FIGS. 28A-D depict an exemplary embodiment of a collet 710 having a headsection 712 and a body section 714. FIG. 28A depicts a three-dimensionalview of collet 710. An end surface of head section 712 has flat portions716 divided into sections by a projecting portion 718. Projection 718has a top surface 720 and a sidewall surface 722 with a hole 723. Amandrel for supporting a stent may be inserted and disposed in hole 723.

Body section 714 has slots 715 running parallel to an axis of bodysection 714. Slots 715 are designed to allow collet 710 to engage andcouple to a rotatable spindle or other support structure. In oneembodiment, body section 714 has six slots 715 spaced 60° apart. Inother embodiments, body section 714 has seven, eight, nine, or tenslots.

FIG. 28B depicts a two-dimensional radial projection of the end surfaceof collet 710 which shows three segments 724 of projection 718 radiatingfrom the center of the end surface of collet 710 to the edge of the endsurface. A thickness 726 of segments 724 of projection 718 decrease fromthe center to the edge of the surface. Adjacent segments 724 may radiatein directions that are 120° apart. Other embodiments may include four,five, or six segments radiating from the center to the edge of the endsurface spaced apart, for example, by 90°, 72°, or 60°, respectively.

FIGS. 28C-D depict side views of collet 710. FIG. 28C depicts a viewthat is parallel to a length of one of segments 724. As shown in FIG.28C, segments 724 have a pitch, θ_(p), which facilitates self-centeringof the stent on the surface of the collet. In one embodiment, θ_(p) canbe 30°. In other embodiments, θ_(p) can be greater than 30°, greaterthan 45°, or greater than 60°. FIG. 28D depicts a view facing along adirection that is between two adjacent segments 724. As shown in FIGS.28A, 28C, and 28D, a height 728 of segments 724 decrease from the centerto the edge of the surface.

In some embodiments, a radius of collet 710 may be sized so that stentends are in contact with segments 724 near the edge of the surface ofthe end of collet 710. Segments 724 are relatively thin near the edge ofthe surface resulting in a relatively small contact area of the stentend with the collet. Thus, wicking of coating material from the stent tocollet 710 is relatively low or nonexistent. Also, defects due tocontact of the stent with collet 710 tend to be reduced or eliminated.Additionally, the decrease in height outward from the center tends toallow the stent to center itself on the surface which results in aconsistent contact area between the stent and collet 710.

An example of collet 710 depicted in FIGS. 28A-D has the followingdimensions: W_(S)=0.10 inch, D_(H)=0.022 inch, D_(B)=0.099 inch,L_(B)=0.22 inch, L_(C)=0.29 inch, and L_(CP)=0.32 inch.

FIGS. 29A-E depict photographs of an embodiment of the collet accordingto the present invention. FIGS. 29A-B depict photographs with side viewsof the collet and FIGS. 29C-D depict photographs with overhead views ofthe collet. FIG. 29E depicts a photograph of a stent mounted on thecollet.

Another aspect of the present invention relates to a method and devicethat reduces operator or machinery contact with a mandrel that supportsa stent during processing. Stent handling or manipulation, whethermanual or automated, risks exposing a stent to damage and/orcontamination with undesired impurities. Embodiments of the presentinvention tend to reduce or eliminate damage to a stent and/or stentcoating that may be caused by handling or manipulation of a stent duringprocessing. Damage can result from contaminants or undesired contactwith surfaces. Such embodiments also reduce or eliminate damageresulting from exposure to a stent to undesired contaminants.

As described above, coating a stent requires a number of processingsteps which involve handling and manipulation of a stent. The processinvolving application of a coating, a drug-polymer coating, for example,may include loading or mounting a stent on a mandrel. A conventionalmandrel for supporting a stent during processing is coupled mechanicallythrough direct or indirect physical contact to fixtures and/or rotatablespindles. For example, mandrel 702 in FIG. 27 is coupled mechanicallythrough direct physical contact to members 708. Such mechanical rotationdevices typically require lubricants or other substances for theirnormal operation. During the course of processing a stent, suchlubricants or substances can come into contact with a coated stent.

Furthermore, as discussed above, a coating is typically applied instages with a drying step in between stages. The application step anddrying step are repeated until a desired weight or loading of coating onthe stent is achieved. After some or all of the drying steps, the stentmay be weighed. When the application-drying stages are completed, thestent is typically dried in an oven to remove all or substantially allof the solvent remaining in the coating.

In conventional coating systems, the above-described procedure canrequire handling and manipulation of a mandrel holding the stent. Forinstance, after application of a coating layer, the mandrel may be movedto a drying station. The drying station, for example, may include anozzle blowing a stream of heated gas on the coated stent. A stent maybe transferred to an oven for a drying, which can be the final dryingstep. In addition, after one or more of the drying steps, a stent may betransferred to a weighing station, unloaded from a mandrel, andtransferred to a scale for weighing. During each of these handling ormanipulation procedures, the stent and/or stent coating can be damagedthrough contact with surfaces or exposure to undesired substances.

Embodiments of a system including a mandrel that can support a stentwithout physical or mechanical contact with other machines or devicesduring processing are described herein. In some embodiments, the mandrelcan contact, hold, translate and/or rotate a stent. Limited operator ormachinery contact with the mandrel reduces or eliminates damage ordefects to a stent and/or stent coating that occur during processing Themandrel of the system is supported, translated, and/or rotated throughmagnetic levitation.

FIG. 30 is an exemplary embodiment of a system 750 having a mandrel 752that is supported by magnetic levitation. Mandrel 752 includes removablecollets 754 and support collets 756. A stent can be placed over mandrel752 between removable collets 754 and supported directly on supportcollets 756. A diameter of support collets 756 can be sized to beslightly smaller than an inside diameter of a stent to be coated.

Mandrel 752 includes permanent magnets 758 embedded within a proximaland a distal end of mandrel 752. “Permanent magnets” refer to materialsthat possess a magnetic field which is not generated by outsideinfluences such as electricity. In some embodiments, mandrel 752 caninclude magnets 758 in only one end of mandrel 752. In otherembodiments, magnets 758 can be embedded or disposed at other positionsalong mandrel 752.

As shown in FIG. 30, mandrel 752 includes three magnets at each end.Generally, a mandrel 752 can include at least one magnet. In someembodiments, mandrel 752 can include more than four or more than fivemagnets. The size, number, and location of the magnets may be modifiedto obtain the desired movement of mandrel 752 as described below.

System 750 further includes electromagnetic coils 760, 761, and 762positioned adjacent to mandrel 752. Coils 760, 761, and 762 areelectrically connected to an electromagnetic power supply 764 whichprovides power to coils 760, 761, and 762 to generate an electricalfield. Electromagnetic coils 760 and 761, for example, generate anelectrical field that allows the magnets 758 to support or levitatemandrel 752 without the physical contact with fixtures or members suchas members 706 and 708 in FIG. 27. The absence of a mechanical couplingbetween mandrel 752 and a support member eliminates the need forlubricants or other substances that may be required and that cancontaminate a stent or stent coating.

Power supply 764 further includes polarity switching equipment. Thepolarity switching equipment induces polarity changes in theelectromagnetic field generated by coils 760, 761, and 762 in a way thatinduces movement of magnets 758 to move mandrel 752 in a selectedmanner. For example, coils 760 and 762 can induce rotation of mandrel752 as shown by an arrow 764 to rotate a stent during application ofcoating material to the stent. Also, coils 762 can induce translation ofmandrel 752 as shown by an arrow 766.

In additional embodiments, a coating system can use magnetic levitationto rotate or translate a stent during or between processing steps. FIG.31 depicts an overhead view of a coating system 800 illustratingstations corresponding to various processing steps. A coating station802 is for application of a coating material, such as a polymer-solventmixture, to a stent. A stent mounted on a mandrel, including magnets,may be rotated and translated under a spray nozzle using magneticlevitation, as described above. Electromagnetic coils for use in themagnetic levitation can be powered by a power supply (not shown).

After application of a coating layer at station 802, the stent can betransferred to a drying station 804 that includes a nozzle that blows astream of heated gas on the coated stent. The stent can be translated toand from station 802 and station 804 as shown by arrows 812 and 813using magnetic levitation induced by coils 810 than run between thestations.

Additionally, the stent can be transferred to a drying station 808 for afinal drying step. Drying station 808 may include an oven for drying thestent. The stent can be translated from station 802 to station 808 asshown by an arrow 814 using magnetic levitation induced by coils 816than run between the stations.

A stent mounted on the mandrel can also be translated, as shown by anarrow 818, using magnetic levitation induced by coils 820 from station804 to a weighing station 806 after the coating on the stent is dried atstation 804. After weighing the stent at weigh station 806, the stentcan then be translated back to coating station 802, as shown by an arrow822, using magnetic levitation induced by coils 824. In addition, thestent can also be translated, as shown by an arrow 826, using magneticlevitation induced by coils 828 from station 808 to weighing station 806after the coating on the stent is dried at station 808.

In other embodiments, a stent loaded on a magnetic mandrel can betranslated to other processing stations or steps than those depicted inFIG. 31.

Purification of Coating Polymers

It is important to control the raw material purity of coating polymersfor medical devices such as stents. A potential problem with polymersused in coating applications of stents is that such polymers can containimpurities that trigger adverse biological responses to the stent whenimplanted into a biological lumen. The polymers can contain impuritiessuch as catalysts, initiators, processing aids, suspension aids,unreacted monomers, and oligomers, or other low molecular weightspecies, even though the polymer is sold as a “medical grade” polymer bythe manufacturer. Thus, there tends to be a need to purify polymers usedin coating applications. Various embodiments of the present inventionrelate to purifying such polymers.

It is desirable that after a polymer has been purified for the polymerto be substantially biologically inert. “Purified” refers to a polymerthat has had impurities removed or significantly reduced. “Impurities”refer to traces of catalysts, initiators, processing aids, suspensionaids, unreacted monomers, and oligomers, or other low molecular weightspecies, or any other chemical remaining in the polymer, that can causeor effectuate an adverse biological response greater than which wouldoccur if the impurity is removed or significantly reduced. For example,“medical grade” poly(n-butyl methacrylate) (PBMA) can contain impuritiessuch as suspension aids (e.g., starch) and unreacted monomers.

“Biologically inert” refers to a material that does not elicit asignificantly greater adverse biological response than a biocompatiblematerial, such as stainless steel, when implanted into a body vessel.Examples of biocompatible materials include metals such as stainlesssteel, titanium, and Nitinol, and organic materials such as collagen,fibronectin, polyethylene glycol, polysaccharides, TEFLON, silicone andpolyurethane.

The coating for a stent including the purified polymer can have adrug-polymer layer, an optional topcoat layer, and an optional primerlayer. The drug-polymer layer can be applied directly onto the stentsurface to serve as a reservoir for a therapeutically active agent ordrug which is incorporated into the drug-polymer layer. The topcoatlayer, which can be essentially free from any therapeutic substances ordrugs, serves as a rate limiting membrane for controlling the rate ofrelease of the drug. The optional primer layer can be applied betweenthe stent and the drug-polymer layer to improve the adhesion of thedrug-polymer layer to the stent.

In one embodiment, poly(vinylidene fluoride-co-hexafluoropropene)copolymer (PVDF-HFP) (e.g., SOLEF 21508, available from Solvay SolexisPVDF, Thorofare, N.J.), can be used as a polymer for a drug-polymerlayer or matrix. Polybutyl methacrylate (PBMA) can be used as the primerto improve adhesion between the metallic stent and the drug-polymerlayer or matrix.

By using the methods described herein, the polymer for the drug-polymerlayer can be purified to remove a significant amount of residualcatalysts, initiators, processing aids, suspension aids, unreactedmonomers, and oligomers or other low molecular weight species. Certainembodiments of a method of purifying a polymer mass may include washingthe polymer mass with a solvent that dissolves an impurity, but not thepolymer. The impurities, such as low molecular species includingunreacted monomers and oligomers, should be miscible or substantiallymiscible in the solvent, while the polymer should be immiscible orsubstantially immiscible in the solvent.

In some embodiments, it may be advantageous for a solvent for use inpurifying PVDF-HFP to have the following properties: (1) capable ofswelling, but not dissolving PVDF-HFP; (2) capable of dissolvingcontaminants such as mineral oil; (3) the boiling temperature is lowenough so that a solvent-washed polymer can be dried without using aconvection oven; and (4) safety—Class III or Class II on theInternational Conference on Harmonization (ICH) Guidance list.

Representative examples of some solvents that may be used to purifyPVDF-HFP include, but are not limited to, acetonitrile (ACN), isopropylalcohol (IPA), methyl acetate (MA), ethyl acetate (EA), isopropylacetate (ISPA), propyl acetate (PA), and mixtures of ethyl acetate andethanol. The suitability of the above solvents for purifying PVDF-HFPcan be evaluated by measuring the swelling of PVDF-HFP and the removalof contaminants from PVDF-HFP. The above-listed solvents werepre-screened by examining the physical parameters listed in Table 3.

TABLE 3 Physical parameters of the solvents evaluated for purificationof PVDF-HFP. EA/EtOH* EA/EtOH EA/EtOH ACN IPA MA EA (75/25) (50/50)(25/75) ISPA PA ICH II III III III III III III III III b.p. 82 82 57 76NA NA NA 87 102 (° C.) Effect Swell Swell Dissolve Dissolve Swell Swellswell swell swell PVDF 40% Mineral <0.02% Not soluble soluble solubleNot Not soluble soluble oil soluble soluble soluble soluble *the boilingpoint for ethanol is 78° C.

Based on the pre-screening data listed in the above table, the followingsolvents were selected for further study of the swell parameters ofPVDF-HFP. These include 1) ACN; 2) IPA; 3) EA; 4) ISPA 5) EA/EtOH(75/25).

The swelling of PVDF-HFP was determined as a function of time. Twomethods were used to measure the PVDF-HFP swell ratio in the solvents:size measurement and weight measurement. Prior to contacting a sample ofPVDF-HFP with a solvent, a sample pellet of PVDF-HFP was weighed andpictures were taken by a light microscope. The diameter of the pelletwas measured from the digital image. This measured diameter is the datafor time zero.

The sample pellet was then placed into a vial containing about 5 gramsof a selected solvent and shaken on a shaker table at 480 rpm. Atselected time intervals, the pellet was taken out for weight and sizemeasurement. By comparing the weight and size of the same pellet at theselected time intervals, the swell parameters of PVDF-HFP in differentsolvents were calculated.

FIG. 32 shows the swell percentage of a polymer sample in each solventtested obtained by measuring the size of the sample at selected times.The swell percentage was calculated by the following formula:(volume(t)−initial volume)/initial volume×100%. The polymer sample inACN had the highest swell percentage or ratio. There was no swelling ofthe polymer sample in the IPA. The polymer sample in the other threesolvents had swell ratios below that of ACN. The swell ratios of thesample for each of solvents appear to flatten out after about 24 hours.Other than acetonitrile, isopropyl acetate and propyl acetate resultedin larger polymer swell for samples than the mixture of ethanol andethyl acetate.

FIG. 33 shows the swell percentage of polymer samples in each solventobtained by measuring the weight at selected times. As above, thepolymer samples had the largest swell ratio in acetonitrile andisopropyl alcohol did not cause any swelling in the polymer sample. Asbefore isopropyl acetate and propyl acetate had a greater effect onpolymer swelling than the mixture of ethanol and ethyl acetate.

FIGS. 32-33 show that the swell percentage obtained from the differentmethods of determining the swell percentage yielded different values ofthe swell percentage. The difference may be due to precision of polymerpellet diameter measurement and the precision of the polymer pelletweight measurement.

The removal of contaminants was studied by analyzing an extractionphase. The extraction phase refers to the mixture of the solvent and anyimpurities or contaminants removed or extracted from the swelled samplepolymer. The extraction phase of acetonitrile, isopropyl acetate, andpropyl acetate was analyzed. The extraction phase was blow-dried with astream of heated gas. The residual remaining after the extraction phasewas blow-dried included contaminants extracted from the polymer sample.The residual was analyzed by Gel Permeation Chromotography (GPC)analysis. Acetone was used to dissolve the residual impurities orcontaminants for the GPC injection. A person of ordinary skill in theart is familiar with the principles of GPC analysis.

The acetonitrile extracted more residual than either isopropyl acetateor propyl acetate. Table 4 lists the results of the GPC analysis of theresidual for each solvent. In Table 4, the “retention time” is thecharacteristic time of passage of a component through a GPC system. Forthe extracts from acetonitrile, a large peak retention time of 19minutes overwrote other small insignificant peaks. For the extractedresidual from isopropyl acetate and propyl acetate, the results showed amixture of small molecular weight and large molecular weight material.The large molecular weight material corresponds to the molecular weightof PVDF-HFP, which is about 280K.

TABLE 4 Results of GPC analysis of extraction phase. Extraction SolventsRetention Time M_(w) of the residual Acetonitrile 19 min 63K IsopropylAcetate 21 min 24K 15 min 288K  Propyl Acetate 21 min 19K 15 min 278K 

Generally, it is desirable to use a solvent to purify PVDF-HVP that (1)swells and extracts a substantial amount of low molecular weightmaterials from the polymer and that (2) dissolves as little as possibleof the polymer. The data indicates that isopropyl acetate has afavorable balance of swelling and extraction with dissolution of thepolymer.

The polymer sample purified by the isopropyl acetate was analyzed afterextraction to determine drying time. The polymer sample was dried in aconvection oven at three different temperatures. The change in weightwas determined using Thermogravimetric Analysis (TGA). Table 5summarizes the results from TGA. The data in Table 3 indicate thatdrying at 85° C. or 90° C. for 24 hours will remove the solvent to anacceptable level.

TABLE 5 Results of TGA analysis of sample purified by isopropyl acetate.Oven Temperature Drying Drop of Weight (° C.) Time in TGA Test Comments80 24 hr 1.17% Polymer looked normal after dry 85 24 hr 0.83% Polymerlooked normal after dry 90 24 hr 0.56% Polymer looked normal after dry

Stent and Coating Materials

A non-polymer substrate for a coating of an implantable medical devicemay be made of a metallic material or an alloy such as, but not limitedto, cobalt chromium alloy (ELGILOY), stainless steel (316L), highnitrogen stainless steel, e.g., BIODUR 108, cobalt chrome alloy L-605,“MP35N,” “MP20N,” ELASTINITE (Nitinol), tantalum, nickel-titanium alloy,platinum-iridium alloy, gold, magnesium, or combinations thereof.“MP35N” and “MP20N” are trade names for alloys of cobalt, nickel,chromium and molybdenum available from Standard Press Steel Co.,Jenkintown, Pa. “MP35N” consists of 35% cobalt, 35% nickel, 20%chromium, and 10% molybdenum. “MP20N” consists of 50% cobalt, 20%nickel, 20% chromium, and 10% molybdenum.

In accordance with one embodiment, the composition can include a solventand a polymer dissolved in the solvent and optionally a wetting fluid.The composition can also include active agents, radiopaque elements, orradioactive isotopes. Representative examples of polymers that may beused as a substrate of a stent or coating for a stent, or moregenerally, implantable medical devices include, but are not limited to,poly(N-acetylglucosamine) (Chitin), Chitosan, poly(3-hydroxyvalerate),poly(lactide-co-glycolide), poly(3-hydroxybutyrate),poly(4-hydroxybutyrate), poly(3-hydroxybutyrate-co-3-hydroxyvalerate),polyorthoester, polyanhydride, poly(glycolic acid), poly(glycolide),poly(L-lactic acid), poly(L-lactide), poly(D,L-lactic acid),poly(D,L-lactide), poly(L-lactide-co-D,L-lactide), poly(caprolactone),poly(L-lactide-co-caprolactone), poly(D,L-lactide-co-caprolactone),poly(glycolide-co-caprolactone), poly(trimethylene carbonate), polyesteramide, poly(glycolic acid-co-trimethylene carbonate),co-poly(ether-esters) (e.g. PEO/PLA), polyphosphazenes, biomolecules(such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid), polyurethanes, silicones, polyesters, polyolefins,polyisobutylene and ethylene-alphaolefin copolymers, acrylic polymersand copolymers, vinyl halide polymers and copolymers (such as polyvinylchloride), polyvinyl ethers (such as polyvinyl methyl ether),polyvinylidene halides (such as polyvinylidene chloride),polyacrylonitrile, polyvinyl ketones, polyvinyl aromatics (such aspolystyrene), polyvinyl esters (such as polyvinyl acetate),acrylonitrile-styrene copolymers, ABS resins, polyamides (such as Nylon66 and polycaprolactam), polycarbonates, polyoxymethylenes, polyimides,polyethers, polyurethanes, rayon, rayon-triacetate, cellulose acetate,cellulose butyrate, cellulose acetate butyrate, cellophane, cellulosenitrate, cellulose propionate, cellulose ethers, and carboxymethylcellulose. Additional representative examples of polymers that may beespecially well suited for use in fabricating embodiments of implantablemedical devices disclosed herein include ethylene vinyl alcoholcopolymer (commonly known by the generic name EVOH or by the trade nameEVAL), poly(butyl methacrylate), poly(vinylidenefluoride-co-hexafluoropropene) (e.g., SOLEF 21508, available from SolvaySolexis PVDF, Thorofare, N.J.), polyvinylidene fluoride (otherwise knownas KYNAR, available from ATOFINA Chemicals, Philadelphia, Pa.),ethylene-vinyl acetate copolymers, poly(vinyl acetate),styrene-isobutylene-styrene triblock copolymers, and polyethyleneglycol.

“Solvent” is defined as a liquid substance or composition that iscompatible with the polymer and is capable of dissolving the polymer atthe concentration desired in the composition. Examples of solventsinclude, but are not limited to, dimethylsulfoxide (DMSO), chloroform,acetone, water (buffered saline), xylene, methanol, ethanol, 1-propanol,tetrahydrofuran, 1-butanone, dimethylformamide, dimethylacetamide,cyclohexanone, ethyl acetate, methylethylketone, propylene glycolmonomethylether, isopropanol, isopropanol admixed with water,N-methylpyrrolidinone, toluene, and combinations thereof.

A “wetting” of a fluid is measured by the fluid's capillary permeation.Capillary permeation is the movement of a fluid on a solid substratedriven by interfacial energetics. Capillary permeation is quantified bya contact angle, defined as an angle at the tangent of a droplet in afluid phase that has taken an equilibrium shape on a solid surface. Alow contact angle means a higher wetting liquid. A suitably highcapillary permeation corresponds to a contact angle less than about 90°.Representative examples of the wetting fluid include, but are notlimited to, tetrahydrofuran (THF), dimethylformamide (DMF), 1-butanol,n-butyl acetate, dimethylacetamide (DMAC), and mixtures and combinationsthereof.

Examples of radiopaque elements include, but are not limited to, gold,tantalum, and platinum. An example of a radioactive isotope is p³².Sufficient amounts of such substances may be dispersed in thecomposition such that the substances are not present in the compositionas agglomerates or flocs.

Active Agents

Examples of active agents include antiproliferative substances such asactinomycin D, or derivatives and analogs thereof (manufactured bySigma-Aldrich 1001 West Saint Paul Avenue, Milwaukee, Wis. 53233; orCOSMEGEN available from Merck). Synonyms of actinomycin D includedactinomycin, actinomycin IV, actinomycin I₁, actinomycin X₁, andactinomycin C₁. The bioactive agent can also fall under the genus ofantineoplastic, anti-inflammatory, antiplatelet, anticoagulant,antifibrin, antithrombin, antimitotic, antibiotic, antiallergic andantioxidant substances. Examples of such antineoplastics and/orantimitotics include paclitaxel, (e.g., TAXOL® by Bristol-Myers SquibbCo., Stamford, Conn.), docetaxel (e.g., Taxotere®, from Aventis S.A.,Frankfurt, Germany), methotrexate, azathioprine, vincristine,vinblastine, fluorouracil, doxorubicin hydrochloride (e.g., Adriamycin®from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g., Mutamycin®from Bristol-Myers Squibb Co., Stamford, Conn.). Examples of suchantiplatelets, anticoagulants, antifibrin, and antithrombins includeaspirin, sodium heparin, low molecular weight heparins, heparinoids,hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax ä (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.,Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g., Prinivil® and Prinzide® from Merck &Co., Inc., Whitehouse Station, N.J.), calcium channel blockers (such asnifedipine), colchicine, proteins, peptides, fibroblast growth factor(FGF) antagonists, fish oil (omega 3-fatty acid), histamine antagonists,lovastatin (an inhibitor of HMG-CoA reductase, a cholesterol loweringdrug, brand name Mevacor® from Merck & Co., Inc., Whitehouse Station,N.J.), monoclonal antibodies (such as those specific forPlatelet-Derived Growth Factor (PDGF) receptors), nitroprusside,phosphodiesterase inhibitors, prostaglandin inhibitors, suramin,serotonin blockers, steroids, thioprotease inhibitors,triazolopyrimidine (a PDGF antagonist), and nitric oxide. An example ofan antiallergic agent is permirolast potassium. Other therapeuticsubstances or agents which may be appropriate agents include cisplatin,insulin sensitizers, receptor tyrosine kinase inhibitors, carboplatin,alpha-interferon, genetically engineered epithelial cells, steroidalanti-inflammatory agents, non-steroidal anti-inflammatory agents,antivirals, anticancer drugs, anticoagulant agents, free radicalscavengers, estradiol, antibiotics, nitric oxide donors, super oxidedismutases, super oxide dismutases mimics,4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl (4-amino-TEMPO),tacrolimus, dexamethasone, ABT-578, clobetasol, cytostatic agents,prodrugs thereof, co-drugs thereof, and a combination thereof. Othertherapeutic substances or agents may include rapamycin and structuralderivatives or functional analogs thereof, such as40-O-(2-hydroxy)ethyl-rapamycin (known by the trade name of EVEROLIMUS),40-O-(3-hydroxy)propyl-rapamycin,40-O-[2-(2-hydroxy)ethoxy]ethyl-rapamycin, methyl rapamycin, and40-O-tetrazole-rapamycin.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects. Therefore, the appended claims are toencompass within their scope all such changes and modifications as fallwithin the true spirit and scope of this invention.

1. A method of drying a stent, comprising: providing a stent in achamber, the stent having a coating material including a polymer and asolvent applied to the stent; directing a fluid stream at the stent toremove at least a portion of the coating material; measuring atemperature of the fluid stream at a location adjacent to the stent; andcontrolling a temperature of the fluid stream based on the measuredtemperature so as to maintain a desired temperature adjacent to thestent, wherein the chamber is configured to receive the stent having thecoating material including the polymer and the solvent and the chamberis adapted to receive the fluid stream that contacts the coated stentfor removing at least a portion of the coating material; a temperaturesensor is adjacent to the stent for measuring a temperature of the fluidstream contacting the stent; a controller is in communication with thesensor, wherein the controller adjusts a temperature of the fluid streambased on the measured temperature so as to maintain a desiredtemperature of the fluid stream contacting the stent; and a secondtemperature sensor is adjacent to the stent for monitoring thetemperature of the stent independent of the controller.
 2. The method ofclaim 1, further comprising measuring a temperature of the fluid streamat a second location adjacent to the stent using the second temperaturesensor.
 3. The method of claim 1, wherein the removed portion of thecoating material comprises the solvent.
 4. The method of claim 1,wherein the chamber has an inlet for receiving the fluid stream and anoutlet where the fluid stream exits, and wherein during the directing ofthe fluid stream at the stent, the stent is positioned between the inletand the outlet on a support structure.
 5. The method of claim 4, whereinthe providing of the stent in the chamber includes inserting the stent,while on the support structure, through an opening of the chamberbetween the inlet and the outlet.
 6. A method of drying a stent,comprising: providing a stent in a chamber, the stent having a coatingmaterial including a polymer and a solvent applied to the stent;directing a fluid stream at the stent to remove at least a portion ofthe coating material; measuring a temperature of the fluid stream at alocation adjacent to the stent; and controlling a temperature of thefluid stream based on the measured temperature so as to maintain adesired temperature adjacent to the stent, wherein the chamber has aninlet for receiving the fluid stream and an outlet where the fluidstream exits, such that the stent is positioned between the inlet andthe outlet on a support structure.
 7. The method of claim 6, wherein theproviding of the stent in the chamber includes inserting the stent,while on the support structure, in an opening of the chamber between theinlet and the outlet.
 8. The method of claim 6, wherein a sensorconducts the measuring of the temperature and the sensor is positionedas close as possible to the stent without disrupting the flow of thefluid stream to the stent and passing the stent.
 9. The method of claim6, wherein removed portion of the coating material comprises thesolvent.
 10. The method of claim 6, the measuring of the temperature ofthe fluid stream at the location adjacent to the stent is performedusing a first temperature sensor, and the method further comprisesmeasuring the temperature of the fluid stream at a second locationadjacent the stent using a second temperature sensor for comparison withthe measurement from the first temperature sensor.
 11. A method ofdrying a stent, comprising: providing a stent in a chamber, the stenthaving a coating material including a polymer and a solvent applied tothe stent; directing a fluid stream at the stent to remove at least aportion of the coating material; measuring a temperature of the fluidstream at a location adjacent to the stent; and controlling atemperature of the fluid stream based on the measured temperature so asto maintain a desired temperature adjacent to the stent, wherein a firsttemperature sensor is in the chamber for measuring a drying temperatureof the stent and communicating the measurement to a controller forcontrolling the drying of the stent, and a second temperature sensor isin the chamber for measuring a drying temperature of the stent anddisplaying the temperature on a monitor.
 12. The method of claim 11,wherein removed portion of the coating material comprises the solvent.13. The method of claim 11, wherein the chamber has an inlet forreceiving the fluid stream and an outlet where the fluid stream exits,and wherein during the directing of the fluid stream at the stent, thestent is positioned between the inlet and the outlet on a supportstructure.
 14. The method of claim 13, wherein the providing of thestent in the chamber includes inserting the stent, while on the supportstructure, through an opening of the chamber between the inlet and theoutlet.
 15. A method of drying a stent, comprising: providing a stent ina chamber, the stent having a coating material including a polymer and asolvent applied to the stent; directing a fluid stream at the stent toremove at least a portion of the coating material; measuring atemperature of the fluid stream at a location adjacent to the stent;controlling a temperature of the fluid stream based on the measuredtemperature so as to maintain a desired temperature adjacent to thestent, the controlling of the temperature of the fluid stream comprisestaking at least one temperature reading from a sensor, providing thereading to a control system such that the control system compares thereading to a selected temperature parameter, and if needed changes thetemperature of the fluid stream based on the comparison made; and usinga second sensor to take at least one temperature reading and displayingit on a monitor for verifying the accuracy of temperature changes madeby the control system.
 16. The method of claim 15, wherein removedportion of the coating material comprises the solvent.
 17. The method ofclaim 15, wherein the chamber has an inlet for receiving the fluidstream and an outlet where the fluid stream exits, and wherein duringthe directing of the fluid stream at the stent, the stent is positionedbetween the inlet and the outlet on a support structure.
 18. The methodof claim 17, wherein the providing of the stent in the chamber includesinserting the stent, while on the support structure, through an openingof the chamber between the inlet and the outlet.